We adopted an intersectionality framework and examined whether the relationship between internalized HIV stigma and depressive symptoms is moderated by internalized substance use stigma. A total of 85 people living with HIV with a history of substance use in the Bronx, New York, completed a survey. Results revealed evidence of moderation: Participants who internalized HIV stigma experienced greater depressive symptoms only if they also internalized substance use stigma. Researchers should examine stigma associated with multiple socially devalued characteristics to best understand how stigma impacts mental health among people living with HIV. Healthcare providers should address stigma associated with the full range of socially devalued characteristics with which people living with HIV live.