Combinations of medications that control HIV viral replication are called antiretroviral therapy (ART). Regimens can be complex, so medication adherence is often suboptimal, although high rates of adherence are necessary for ART to be effective. Social support, which has been directly and indirectly associated with better treatment adherence in HIV-infected individuals, influences negative affect, including depression and anxiety. Our study assessed whether current anxious and depressive symptoms mediated the relationship between general social support and recent self-reported medication adherence in HIV-infected men who have sex with men (N = 136; 65% White, 15% Black/African American). Results revealed no direct effect, but an indirect effect of depressive (95% CI [-.011, -.0011]) and anxious symptoms (95% CI [-.0097, -.0009]), between social support and medication adherence. Greater levels of social support were associated with lower levels of depression and anxiety, which in turn were associated with lower ART adherence.