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

    <schemaVersion>X0508</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2025-12-12</periodOfReport>

    <notSubjectToSection16>0</notSubjectToSection16>

    <issuer>
        <issuerCik>0001855485</issuerCik>
        <issuerName>Calidi Biotherapeutics, Inc.</issuerName>
        <issuerTradingSymbol>CLDI</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001990674</rptOwnerCik>
            <rptOwnerName>Camaisa Allan</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O CALIDI BIOTHERAPEUTICS, INC.</rptOwnerStreet1>
            <rptOwnerStreet2>4475 EXECUTIVE DRIVE, SUITE 200</rptOwnerStreet2>
            <rptOwnerCity>SAN DIEGO,</rptOwnerCity>
            <rptOwnerState>CA</rptOwnerState>
            <rptOwnerZipCode>92121</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle></officerTitle>
            <otherText></otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>0</aff10b5One>

    <nonDerivativeTable>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
                <footnoteId id="F5"/>
            </securityTitle>
            <transactionDate>
                <value>2025-12-12</value>
            </transactionDate>
            <deemedExecutionDate></deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>S</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
            </transactionCoding>
            <transactionTimeliness></transactionTimeliness>
            <transactionAmounts>
                <transactionShares>
                    <value>850</value>
                    <footnoteId id="F1"/>
                </transactionShares>
                <transactionPricePerShare>
                    <value>1.455</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>76952</value>
                    <footnoteId id="F2"/>
                    <footnoteId id="F3"/>
                    <footnoteId id="F4"/>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>AJC Capital, LLC</value>
                    <footnoteId id="F4"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
    </nonDerivativeTable>

    <footnotes>
        <footnote id="F1">The sales reported in this Form 4 were effected for estate and tax planning purposes by AJC Capital, LLC (&quot;AJC&quot;). The reporting person undertakes to provide full information regarding the number of shares and prices at which the transactions were effected upon request of the SEC staff, the Issuer or a security holder of the Issuer.</footnote>
        <footnote id="F2">Includes (i) 6,394 shares of Common Stock directly held by Allan Camaisa, (ii) 19,860 shares of Common Stock held by AJC, and (iii) 50,698 shares of Common Stock held by Jamir Trust.</footnote>
        <footnote id="F3">Does not include, (i) 1,526 shares of Common Stock issuable upon exercise of vested options within sixty (60) days held by Mr. Camaisa, (ii) 3,915 shares of Common Stock issuable upon exercise of warrants within sixty (60) days held by Mr. Camaisa, and (iii) 22,887 shares of Common Stock issuable upon exercise of vested options within sixty (60) days held by AJC.</footnote>
        <footnote id="F4">Mr. Camaisa is the sole managing member and owner of AJC and the sole trustee of Jamir Trust; as such, Mr. Camaisa is deemed to have beneficial ownership of the Common Stock held by AJC and Jamir Trust.</footnote>
        <footnote id="F5">All share and share related information gives retrospective effect to the 1-for-12 reverse stock split effective on August 4, 2025.</footnote>
    </footnotes>

    <ownerSignature>
        <signatureName>/s/ Andrew Jackson, Attorney-in-fact</signatureName>
        <signatureDate>2025-12-16</signatureDate>
    </ownerSignature>
</ownershipDocument>
