Individuals living with HIV experience higher rates of stigmatizing social interactions that may negatively impact psychological and physical health. We examined depressive symptoms as a mediator of the relationship between HIV-specific unsupportive social interactions (USIs) and health behaviors in 87 Black and White men living with HIV (MLWH). We also examined ethnicity as a moderator of this model. Depressive symptoms were an indirect mechanism through which HIV-specific USIs explained poorer health behaviors. The indirect effects between disconnecting USI, more depressive symptoms, and poorer health behaviors were significant for Black men but not for White men. Depressive symptoms may be one pathway through which USI are associated with physical health, and disconnecting USI may be particularly detrimental for Black MLWH.