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    <schemaVersion>X0708</schemaVersion>

    <submissionType>D</submissionType>

    <testOrLive>LIVE</testOrLive>

    <primaryIssuer>
        <cik>0001907685</cik>
        <entityName>Comera Life Sciences Holdings, Inc.</entityName>
        <issuerAddress>
            <street1>12 GILL STREET</street1>
            <street2>SUITE 4650</street2>
            <city>WOBURN</city>
            <stateOrCountry>MA</stateOrCountry>
            <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
            <zipCode>01801</zipCode>
        </issuerAddress>
        <issuerPhoneNumber>(617)871-2101</issuerPhoneNumber>
        <jurisdictionOfInc>DELAWARE</jurisdictionOfInc>
        <issuerPreviousNameList>
            <value>None</value>
        </issuerPreviousNameList>
        <edgarPreviousNameList>
            <value>None</value>
        </edgarPreviousNameList>
        <entityType>Corporation</entityType>
        <yearOfInc>
            <withinFiveYears>true</withinFiveYears>
            <value>2022</value>
        </yearOfInc>
    </primaryIssuer>

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        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Michael</firstName>
                <middleName>Gerard</middleName>
                <lastName>Campbell</lastName>
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                <street2>12 Gill Street, Suite 4650</street2>
                <city>Woburn</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>01801</zipCode>
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            <relatedPersonRelationshipList>
                <relationship>Executive Officer</relationship>
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            <relationshipClarification></relationshipClarification>
        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Jeffrey</firstName>
                <middleName>S.</middleName>
                <lastName>Hackman</lastName>
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                <street1>c/o Comera Life Sciences Holdings, Inc.</street1>
                <street2>12 Gill Street, Suite 4650</street2>
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                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>01801</zipCode>
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                <relationship>Director</relationship>
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                <firstName>Neal</firstName>
                <lastName>Muni</lastName>
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                <street1>c/o Comera Life Sciences Holdings, Inc.</street1>
                <street2>12 Gill Street, Suite 4650</street2>
                <city>Woburn</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>01801</zipCode>
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                <middleName>Patrick</middleName>
                <lastName>Mahoney</lastName>
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                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>01801</zipCode>
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        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Janice</firstName>
                <middleName>Marie</middleName>
                <lastName>McCourt</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>c/o Comera Life Sciences Holdings, Inc.</street1>
                <street2>12 Gill Street, Suite 4650</street2>
                <city>Woburn</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>01801</zipCode>
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            <relatedPersonRelationshipList>
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                <firstName>James</firstName>
                <lastName>Sherblom</lastName>
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                <street2>12 Gill Street, Suite 4650</street2>
                <city>Woburn</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
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        <relatedPersonInfo>
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                <firstName>Stuart</firstName>
                <middleName>A.</middleName>
                <lastName>Randle</lastName>
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                <zipCode>01801</zipCode>
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        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Edward</firstName>
                <middleName>Aloysius</middleName>
                <lastName>Sullivan Jr.</lastName>
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            <relatedPersonAddress>
                <street1>c/o Comera Life Sciences Holdings, Inc.</street1>
                <street2>12 Gill Street, Suite 4650</street2>
                <city>Woburn</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>01801</zipCode>
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            <relatedPersonName>
                <firstName>Sirshendu</firstName>
                <middleName>Roopom</middleName>
                <lastName>Banerjee</lastName>
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        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Kirsten</firstName>
                <lastName>Flowers</lastName>
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                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>01801</zipCode>
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            <relatedPersonRelationshipList>
                <relationship>Director</relationship>
            </relatedPersonRelationshipList>
            <relationshipClarification></relationshipClarification>
        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>William</firstName>
                <middleName>A.</middleName>
                <lastName>Wexler</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>c/o Comera Life Sciences Holdings, Inc.</street1>
                <street2>12 Gill Street, Suite 4650</street2>
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                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>01801</zipCode>
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            <relatedPersonRelationshipList>
                <relationship>Director</relationship>
            </relatedPersonRelationshipList>
            <relationshipClarification></relationshipClarification>
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    <offeringData>
        <industryGroup>
            <industryGroupType>Biotechnology</industryGroupType>
        </industryGroup>
        <issuerSize>
            <revenueRange>Decline to Disclose</revenueRange>
        </issuerSize>
        <federalExemptionsExclusions>
            <item>06b</item>
        </federalExemptionsExclusions>
        <typeOfFiling>
            <newOrAmendment>
                <isAmendment>false</isAmendment>
            </newOrAmendment>
            <dateOfFirstSale>
                <value>2023-01-04</value>
            </dateOfFirstSale>
        </typeOfFiling>
        <durationOfOffering>
            <moreThanOneYear>false</moreThanOneYear>
        </durationOfOffering>
        <typesOfSecuritiesOffered>
            <isEquityType>true</isEquityType>
            <isOptionToAcquireType>true</isOptionToAcquireType>
            <isSecurityToBeAcquiredType>true</isSecurityToBeAcquiredType>
        </typesOfSecuritiesOffered>
        <businessCombinationTransaction>
            <isBusinessCombinationTransaction>false</isBusinessCombinationTransaction>
            <clarificationOfResponse></clarificationOfResponse>
        </businessCombinationTransaction>
        <minimumInvestmentAccepted>0</minimumInvestmentAccepted>
        <salesCompensationList></salesCompensationList>
        <offeringSalesAmounts>
            <totalOfferingAmount>3561250</totalOfferingAmount>
            <totalAmountSold>3561250</totalAmountSold>
            <totalRemaining>0</totalRemaining>
            <clarificationOfResponse>Figures in this Item 13 do not include amounts the Company may receive upon the exercise of the warrants in the future, if any.</clarificationOfResponse>
        </offeringSalesAmounts>
        <investors>
            <hasNonAccreditedInvestors>false</hasNonAccreditedInvestors>
            <totalNumberAlreadyInvested>14</totalNumberAlreadyInvested>
        </investors>
        <salesCommissionsFindersFees>
            <salesCommissions>
                <dollarAmount>0</dollarAmount>
            </salesCommissions>
            <findersFees>
                <dollarAmount>0</dollarAmount>
            </findersFees>
            <clarificationOfResponse></clarificationOfResponse>
        </salesCommissionsFindersFees>
        <useOfProceeds>
            <grossProceedsUsed>
                <dollarAmount>0</dollarAmount>
            </grossProceedsUsed>
            <clarificationOfResponse></clarificationOfResponse>
        </useOfProceeds>
        <signatureBlock>
            <authorizedRepresentative>false</authorizedRepresentative>
            <signature>
                <issuerName>Comera Life Sciences Holdings, Inc.</issuerName>
                <signatureName>/s/ Michael Campbell</signatureName>
                <nameOfSigner>Michael Campbell</nameOfSigner>
                <signatureTitle>EVP and CFO</signatureTitle>
                <signatureDate>2023-01-12</signatureDate>
            </signature>
        </signatureBlock>
    </offeringData>
</edgarSubmission>
