Psychosocial support services are essential for effective HIV care, yet this area remains under-researched in sub-Saharan settings where the HIV epidemic is the most devastating. We explored the relationships between social support, perceived stigma, and quality of life (QOL) in HIV-positive adults participating in a family-centered pediatric HIV care and treatment program in Kinshasa, Democratic Republic of Congo (DRC). Baseline interviews were conducted with 275 HIV-positive adults who were caregivers or first-line relatives of enrolled HIV-positive children. Associations between variables were examined using Pearson correlation coefficients. Hierarchical multiple regression was used to test the hypothesis that the relationship of social support to QOL was moderated by perceived stigma. We examined psychological status, which overlaps with symptoms of depression and is one of the six domains in the World Health Organization (WHO) QOL measure, separately and as part of overall QOL. Our sample was 84% female and largely mothers with relatively little formal education. There was a positive association between social support and psychological status (r?=?0.42(224), p < 0.001) and a negative association between perceived stigma and psychological status (r = –0.31(226), p < 0.001). The relationship of social support to psychological status was moderated by perceived stigma (? = 0.191, p < 0.05) such that the association between social support and psychological status was positive and stronger for patients reporting high stigma than for patients reporting low stigma. The relationship of social support to overall QOL was not moderated by perceived stigma (? = 0.089, p?=?0.397). These results highlight the importance of assessing multiple QOL domains. By examining psychological status separately, we found support for our hypothesis which we would not have found if only overall QOL had been examined. Enhancing social support may be particularly important for those reporting high stigma in improving QOL. As access to antiretroviral therapy increases, so does the relevance of modifiable predictors of QOL.