Persons living with HIV in the United States face social stigma related to their health conditions. The present study evaluated the relationship between concerns about HIV-related stigma, quality of life, and social support and evaluated social support as a possible pathway contributing to the relationship between stigma concerns and quality of life in low-income Hispanics living with HIV (N = 160). Persons who expressed greater HIV-related stigma concerns in the context of receiving medical care reported poorer psychological functioning (R2 delta = .08, P < .01), lower physical functioning (R2 delta = .03, P < .05), and a decreased ability to complete daily activities (R2 delta = .06, P < .01). In addition, higher levels of stigma concerns were associated with lower social support (R2 delta = .15, P < .001). Mediation analyses showed that social support accounted, in part, for the relationship between stigma concerns and physical functioning (z = 2.16, P < .05), psychological functioning (z = 3.18, P < .001), and interference with daily activities (z = 2.95, P < .01). Interventions directed toward dispelling HIV-related social stigma by educating patients, communities, and physicians would be beneficial to improve quality of life in Hispanics living with HIV.