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

    <schemaVersion>X0306</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2021-09-08</periodOfReport>

    <issuer>
        <issuerCik>0001786248</issuerCik>
        <issuerName>NexPoint Real Estate Finance, Inc.</issuerName>
        <issuerTradingSymbol>NREF</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001636187</rptOwnerCik>
            <rptOwnerName>McGraner Matt</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>300 CRESCENT COURT, SUITE 700</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>DALLAS</rptOwnerCity>
            <rptOwnerState>TX</rptOwnerState>
            <rptOwnerZipCode>75201</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isOfficer>1</isOfficer>
            <officerTitle>See Remarks</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>OP Units</value>
                <footnoteId id="F1"/>
            </securityTitle>
            <conversionOrExercisePrice>
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            <transactionDate>
                <value>2021-09-08</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>14108.35</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                    <footnoteId id="F3"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>14108.35</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>0</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnote</value>
                    <footnoteId id="F4"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>OP Units</value>
                <footnoteId id="F1"/>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F2"/>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2021-09-08</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>126975.17</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                    <footnoteId id="F3"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>126975.17</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>0</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnote</value>
                    <footnoteId id="F4"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>Class C OP Units</value>
                <footnoteId id="F1"/>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F2"/>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2021-09-08</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>14108.35</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                    <footnoteId id="F3"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
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            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>14108.35</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>14108.35</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnote</value>
                    <footnoteId id="F5"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>Class C OP Units</value>
                <footnoteId id="F1"/>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F2"/>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2021-09-08</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
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            <transactionAmounts>
                <transactionShares>
                    <value>126975.17</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                    <footnoteId id="F3"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>126975.17</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>126975.17</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnote</value>
                    <footnoteId id="F5"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Represents common units of limited partnership interest (&quot;OP Units&quot;) in NexPoint Real Estate Finance Operating Partnership, L.P., the operating partnership (the &quot;OP&quot;) of NexPoint Real Estate Finance, Inc. (the &quot;Issuer&quot;).</footnote>
        <footnote id="F2">The OP Units are redeemable, subject to certain requirements, for cash or, at the election of the Issuer, for shares of the Issuer's common stock on a one-for-one basis. The OP Units were vested as of the date of issuance and have no expiration date.</footnote>
        <footnote id="F3">Pursuant to a reclassification exempt under Rule 16b-7 promulgated under the Securities Exchange Act of 1934, as amended (the &quot;Exchange Act&quot;), each OP Unit reported herein was reclassified into a new Class C OP Unit.</footnote>
        <footnote id="F4">Prior to the reclassification referred to in footnote 3 hereto, Mr. McGraner transferred 126,975.17 OP Units to another trust for which he serves as trustee.</footnote>
        <footnote id="F5">These OP Units are held by trusts for which Mr. McGraner serves as trustee. Mr. McGraner disclaims beneficial ownership of such OP Units except to the extent of his pecuniary interest therein.</footnote>
    </footnotes>

    <remarks>Executive VP and Chief Investment Officer</remarks>

    <ownerSignature>
        <signatureName>/s/ Brian Mitts, as attorney-in-fact for Matt McGraner</signatureName>
        <signatureDate>2021-11-12</signatureDate>
    </ownerSignature>
</ownershipDocument>
