<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2023-12-27</periodOfReport>

    <noSecuritiesOwned>0</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001907685</issuerCik>
        <issuerName>Comera Life Sciences Holdings, Inc.</issuerName>
        <issuerTradingSymbol>CMRA</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001234950</rptOwnerCik>
            <rptOwnerName>HALPERN JOHN D</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>PO BOX 540</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>PORTSMOUTH</rptOwnerCity>
            <rptOwnerState>NH</rptOwnerState>
            <rptOwnerZipCode>03802</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>1</isOther>
            <otherText>Member of 10% owner group</otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001862932</rptOwnerCik>
            <rptOwnerName>Halpern Katherine H.</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>P.O. BOX 540</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>PORTSMOUTH</rptOwnerCity>
            <rptOwnerState>NH</rptOwnerState>
            <rptOwnerZipCode>03802</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>1</isOther>
            <otherText>Member of 10% owner group</otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <nonDerivativeTable>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>1088819</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Trust</value>
                    <footnoteId id="F1"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
    </nonDerivativeTable>

    <derivativeTable>
        <derivativeHolding>
            <securityTitle>
                <value>Warrants to Purchase Common Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>1.23</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <value>2023-01-02</value>
            </exerciseDate>
            <expirationDate>
                <value>2028-01-02</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>405404</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Trust</value>
                    <footnoteId id="F1"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Warrants to Purchase Common Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>0.6135</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <value>2024-02-01</value>
            </exerciseDate>
            <expirationDate>
                <value>2028-07-31</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>855745</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Trust</value>
                    <footnoteId id="F1"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Warrants to Purchase Common Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>0.6135</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <value>2023-09-11</value>
            </exerciseDate>
            <expirationDate>
                <value>2028-09-11</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>366748</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Trust</value>
                    <footnoteId id="F1"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Warrants to Purchase Common Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>0.055</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <value>2023-12-29</value>
            </exerciseDate>
            <expirationDate>
                <value>2028-12-29</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>4073744</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Trust</value>
                    <footnoteId id="F1"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>12.0% Senior Secured Convertible Notes</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>0.055</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <value>2023-12-29</value>
            </exerciseDate>
            <expirationDate>
                <value>2024-12-29</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>2036872</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Trust</value>
                    <footnoteId id="F1"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeHolding>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Held by John D. Halpern Revocable Trust, of which both John D. Halpern and Katherine H. Halpern are trustees.</footnote>
    </footnotes>

    <ownerSignature>
        <signatureName>/s/ John D. Halpern</signatureName>
        <signatureDate>2024-01-08</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>/s/ Katherine H. Halpern</signatureName>
        <signatureDate>2024-01-08</signatureDate>
    </ownerSignature>
</ownershipDocument>
