The authors explored the quality of life (QOL) and psychological distress of HIV-positive persons in a city in South India. The 309 HIV-positive adults were administered the World Health Organization Quality of Life–BREF and the Depression Anxiety and Stress Scale (DASS). Data analysis revealed no significant sex-based difference on all dimensions of QOL but significantly higher depression and stress scores for female respondents. Further, all subdimensions of QOL showed highly significant negative correlations with the overall DASS score and its subdimensions. Following regression analysis, the total DASS score emerged as a significant predictor of QOL. Findings indicate areas for intervention that merit attention.