Research has not yet examined the relationship between psychological need satisfaction, sleep, mindfulness, and health-related quality of life in people living with HIV. This cross-sectional study (N = 101; 84% male; mean age = 45.48, SD = 12.75) found need satisfaction to relate positively to physical and mental health. Sleep quality fully mediated the association with physical health and partially mediated the association with mental health. Furthermore, mindfulness related to higher sleep quality through higher need satisfaction. Findings underscore the role of need satisfaction in determining health-related quality of life and sleep quality in people living with HIV and suggest that mindfulness may facilitate need satisfaction.