<?xml version="1.0" encoding="us-ascii"?>
<!-- DFIN ActiveDisclosure(SM) XBRL Linkbase Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date      : 2020-11-10T15:11:06.2781001+00:00 -->
<!-- Version            : 5.0.1.513 -->
<!-- Package ID         : b106ef05527d4a4e98925e49e04f5dae -->
<!-- Copyright (c) 2020 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef xlink:type="simple" xlink:href="eq-20200930.xsd#TemplateLink" roleURI="http://equilliumbio.com/20200930/role/TemplateLink" />
  <link:roleRef roleURI="http://equilliumbio.com/20200930/taxonomy/role/StatementCondensedConsolidatedBalanceSheets" xlink:href="eq-20200930.xsd#Role_StatementCondensedConsolidatedBalanceSheets" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://equilliumbio.com/20200930/taxonomy/role/StatementCondensedConsolidatedBalanceSheets">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent" xlink:type="locator" xlink:label="us-gaap_PrepaidExpenseAndOtherAssetsCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:type="locator" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:type="locator" xlink:label="us-gaap_OtherAssetsNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:type="locator" xlink:label="us-gaap_PropertyPlantAndEquipmentNet" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AssetsCurrent" xlink:type="locator" xlink:label="us-gaap_AssetsCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Assets" xlink:type="locator" xlink:label="us-gaap_Assets" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NotesPayableCurrent" xlink:type="locator" xlink:label="us-gaap_NotesPayableCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_AccruedLiabilitiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:type="locator" xlink:label="us-gaap_AccountsPayableCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:type="locator" xlink:label="us-gaap_OtherLiabilitiesNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermNotesPayable" xlink:type="locator" xlink:label="us-gaap_LongTermNotesPayable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_LiabilitiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:type="locator" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:type="locator" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:type="locator" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockValue" xlink:type="locator" xlink:label="us-gaap_CommonStockValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockholdersEquity" xlink:type="locator" xlink:label="us-gaap_StockholdersEquity" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommitmentsAndContingencies" xlink:type="locator" xlink:label="us-gaap_CommitmentsAndContingencies" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Liabilities" xlink:type="locator" xlink:label="us-gaap_Liabilities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:type="locator" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_Liabilities" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_CommitmentsAndContingencies" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_StockholdersEquity" order="10030.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_CommonStockValue" order="10040.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_AdditionalPaidInCapitalCommonStock" order="10050.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" order="10060.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit" order="10070.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities" xlink:to="us-gaap_LiabilitiesCurrent" order="10080.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities" xlink:to="us-gaap_LongTermNotesPayable" order="10090.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities" xlink:to="us-gaap_OtherLiabilitiesNoncurrent" order="10100.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_AccountsPayableCurrent" order="10110.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_AccruedLiabilitiesCurrent" order="10120.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_NotesPayableCurrent" order="10130.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsCurrent" order="10140.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" order="10150.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OtherAssetsNoncurrent" order="10160.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue" order="10170.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" order="10180.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_PrepaidExpenseAndOtherAssetsCurrent" order="10190.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://equilliumbio.com/20200930/taxonomy/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLossUnaudited" xlink:href="eq-20200930.xsd#Role_StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLossUnaudited" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://equilliumbio.com/20200930/taxonomy/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLossUnaudited">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GeneralAndAdministrativeExpense" xlink:type="locator" xlink:label="us-gaap_GeneralAndAdministrativeExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingExpenses" xlink:type="locator" xlink:label="us-gaap_OperatingExpenses" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:type="locator" xlink:label="us-gaap_OtherNonoperatingIncomeExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InvestmentIncomeInterest" xlink:type="locator" xlink:label="us-gaap_InvestmentIncomeInterest" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InterestExpenseDebt" xlink:type="locator" xlink:label="us-gaap_InterestExpenseDebt" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NonoperatingIncomeExpense" xlink:type="locator" xlink:label="us-gaap_NonoperatingIncomeExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:type="locator" xlink:label="us-gaap_OperatingIncomeLoss" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" xlink:type="locator" xlink:label="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodBeforeTax" xlink:type="locator" xlink:label="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodBeforeTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTax" xlink:type="locator" xlink:label="us-gaap_OtherComprehensiveIncomeLossNetOfTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetIncomeLoss" xlink:type="locator" xlink:label="us-gaap_NetIncomeLoss" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:type="locator" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_NetIncomeLoss" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeLossNetOfTax" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodBeforeTax" order="10030.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" order="10040.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss" order="10050.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss" xlink:to="us-gaap_NonoperatingIncomeExpense" order="10060.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense" xlink:to="us-gaap_InterestExpenseDebt" order="10070.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense" xlink:to="us-gaap_InvestmentIncomeInterest" order="10080.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense" xlink:to="us-gaap_OtherNonoperatingIncomeExpense" order="10090.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss" xlink:to="us-gaap_OperatingExpenses" order="10100.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses" xlink:to="us-gaap_ResearchAndDevelopmentExpense" order="10110.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses" xlink:to="us-gaap_GeneralAndAdministrativeExpense" order="10120.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://equilliumbio.com/20200930/taxonomy/role/StatementCondensedConsolidatedStatementsOfCashFlowsUnaudited" xlink:href="eq-20200930.xsd#Role_StatementCondensedConsolidatedStatementsOfCashFlowsUnaudited" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://equilliumbio.com/20200930/taxonomy/role/StatementCondensedConsolidatedStatementsOfCashFlowsUnaudited">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities" xlink:type="locator" xlink:label="us-gaap_IncreaseDecreaseInAccruedLiabilities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:type="locator" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:type="locator" xlink:label="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:type="locator" xlink:label="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GainOnSaleOfInvestments" xlink:type="locator" xlink:label="us-gaap_GainOnSaleOfInvestments" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AmortizationOfFinancingCostsAndDiscounts" xlink:type="locator" xlink:label="us-gaap_AmortizationOfFinancingCostsAndDiscounts" />
    <link:loc xlink:href="eq-20200930.xsd#eq_NonCashConsultingExpense" xlink:type="locator" xlink:label="eq_NonCashConsultingExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ForeignCurrencyTransactionGainLossUnrealized" xlink:type="locator" xlink:label="us-gaap_ForeignCurrencyTransactionGainLossUnrealized" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensation" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DepreciationAndAmortization" xlink:type="locator" xlink:label="us-gaap_DepreciationAndAmortization" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProfitLoss" xlink:type="locator" xlink:label="us-gaap_ProfitLoss" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfShorttermInvestments" xlink:type="locator" xlink:label="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfShorttermInvestments" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquireShortTermInvestments" xlink:type="locator" xlink:label="us-gaap_PaymentsToAcquireShortTermInvestments" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:type="locator" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromStockPlans" xlink:type="locator" xlink:label="us-gaap_ProceedsFromStockPlans" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromDebtNetOfIssuanceCosts" xlink:type="locator" xlink:label="us-gaap_ProceedsFromDebtNetOfIssuanceCosts" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:type="locator" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:type="locator" xlink:label="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:type="locator" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:type="locator" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:type="locator" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:type="locator" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities" order="10030.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" order="10040.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock" order="10050.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_ProceedsFromDebtNetOfIssuanceCosts" order="10070.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_ProceedsFromStockPlans" order="10080.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" order="10090.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_PaymentsToAcquireShortTermInvestments" order="10100.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfShorttermInvestments" order="10110.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_ProfitLoss" order="10120.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_DepreciationAndAmortization" order="10130.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_ShareBasedCompensation" order="10140.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_ForeignCurrencyTransactionGainLossUnrealized" order="10150.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="eq_NonCashConsultingExpense" order="10160.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_AmortizationOfFinancingCostsAndDiscounts" order="10170.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_GainOnSaleOfInvestments" order="10180.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments" order="10190.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" order="10200.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayable" order="10210.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInAccruedLiabilities" order="10220.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://equilliumbio.com/20200930/taxonomy/role/DisclosureCertainFinancialStatementCaptionInformationScheduleOfCompanySShortTermInvestmentsDetails" xlink:href="eq-20200930.xsd#Role_DisclosureCertainFinancialStatementCaptionInformationScheduleOfCompanySShortTermInvestmentsDetails" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://equilliumbio.com/20200930/taxonomy/role/DisclosureCertainFinancialStatementCaptionInformationScheduleOfCompanySShortTermInvestmentsDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" order="10010.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" order="10030.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://equilliumbio.com/20200930/taxonomy/role/DisclosureCertainFinancialStatementCaptionInformationScheduleOfAccruedExpensesDetails" xlink:href="eq-20200930.xsd#Role_DisclosureCertainFinancialStatementCaptionInformationScheduleOfAccruedExpensesDetails" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://equilliumbio.com/20200930/taxonomy/role/DisclosureCertainFinancialStatementCaptionInformationScheduleOfAccruedExpensesDetails">
    <link:loc xlink:href="eq-20200930.xsd#eq_AccruedPreclinicalResearch" xlink:type="locator" xlink:label="eq_AccruedPreclinicalResearch" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InterestPayableCurrent" xlink:type="locator" xlink:label="us-gaap_InterestPayableCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherAccruedLiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent" />
    <link:loc xlink:href="eq-20200930.xsd#eq_AccruedClinicalStudies" xlink:type="locator" xlink:label="eq_AccruedClinicalStudies" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_AccruedLiabilitiesCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="eq_AccruedClinicalStudies" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_OtherAccruedLiabilitiesCurrent" order="10030.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_InterestPayableCurrent" order="10040.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="eq_AccruedPreclinicalResearch" order="10050.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://equilliumbio.com/20200930/taxonomy/role/DisclosureNotesPayableScheduleOfAggregateCarryingAmountsOfTermLoansDetails" xlink:href="eq-20200930.xsd#Role_DisclosureNotesPayableScheduleOfAggregateCarryingAmountsOfTermLoansDetails" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://equilliumbio.com/20200930/taxonomy/role/DisclosureNotesPayableScheduleOfAggregateCarryingAmountsOfTermLoansDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscount" xlink:type="locator" xlink:label="us-gaap_DebtInstrumentUnamortizedDiscount" />
    <link:loc xlink:href="eq-20200930.xsd#eq_AccretedLiabilityForFinalPaymentFee" xlink:type="locator" xlink:label="eq_AccretedLiabilityForFinalPaymentFee" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:type="locator" xlink:label="us-gaap_DebtInstrumentCarryingAmount" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt" xlink:type="locator" xlink:label="us-gaap_LongTermDebt" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_DebtInstrumentCarryingAmount" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="eq_AccretedLiabilityForFinalPaymentFee" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_DebtInstrumentUnamortizedDiscount" order="10030.00" priority="2" use="optional" weight="-1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://equilliumbio.com/20200930/taxonomy/role/DisclosureNotesPayableScheduleFutureMaturitiesOfTermLoansIncludingFinalPaymentFeeDetails" xlink:href="eq-20200930.xsd#Role_DisclosureNotesPayableScheduleFutureMaturitiesOfTermLoansIncludingFinalPaymentFeeDetails" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://equilliumbio.com/20200930/taxonomy/role/DisclosureNotesPayableScheduleFutureMaturitiesOfTermLoansIncludingFinalPaymentFeeDetails">
    <link:loc xlink:href="eq-20200930.xsd#eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearFive" xlink:type="locator" xlink:label="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearFive" />
    <link:loc xlink:href="eq-20200930.xsd#eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearFour" xlink:type="locator" xlink:label="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearFour" />
    <link:loc xlink:href="eq-20200930.xsd#eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearThree" xlink:type="locator" xlink:label="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearThree" />
    <link:loc xlink:href="eq-20200930.xsd#eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:type="locator" xlink:label="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearTwo" />
    <link:loc xlink:href="eq-20200930.xsd#eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear" xlink:type="locator" xlink:label="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscount" xlink:type="locator" xlink:label="us-gaap_DebtInstrumentUnamortizedDiscount" />
    <link:loc xlink:href="eq-20200930.xsd#eq_UnaccretedLiabilityForFinalPaymentFee" xlink:type="locator" xlink:label="eq_UnaccretedLiabilityForFinalPaymentFee" />
    <link:loc xlink:href="eq-20200930.xsd#eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFee" xlink:type="locator" xlink:label="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFee" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt" xlink:type="locator" xlink:label="us-gaap_LongTermDebt" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFee" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="eq_UnaccretedLiabilityForFinalPaymentFee" order="10020.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_DebtInstrumentUnamortizedDiscount" order="10030.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFee" xlink:to="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear" order="10040.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFee" xlink:to="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearTwo" order="10050.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFee" xlink:to="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearThree" order="10060.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFee" xlink:to="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearFour" order="10070.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFee" xlink:to="eq_DebtInstrumentCarryingAmountIncludingUnaccretedLiabilityForFinalPaymentFeeMaturitiesRepaymentsOfPrincipalInYearFive" order="10080.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://equilliumbio.com/20200930/taxonomy/role/DisclosureNotesPayableScheduleFutureMaturitiesOfTermLoansIncludingFinalPaymentFeeDetails2" xlink:href="eq-20200930.xsd#Role_DisclosureNotesPayableScheduleFutureMaturitiesOfTermLoansIncludingFinalPaymentFeeDetails2" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://equilliumbio.com/20200930/taxonomy/role/DisclosureNotesPayableScheduleFutureMaturitiesOfTermLoansIncludingFinalPaymentFeeDetails2">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtNoncurrent" xlink:type="locator" xlink:label="us-gaap_LongTermDebtNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtCurrent" xlink:type="locator" xlink:label="us-gaap_LongTermDebtCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt" xlink:type="locator" xlink:label="us-gaap_LongTermDebt" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_LongTermDebtCurrent" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_LongTermDebtNoncurrent" order="10020.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
</link:linkbase>
