Increasing quality of life (QoL) is both an end in itself and a means to optimize the impact of treatment in HIV-infected persons. Possibly due to cultural and social influences, the predictors of QoL vary across studies, highlighting the importance of studying specific populations. In the present study, we aimed to determine the sociodemographic (age, sex and schooling, or number of years at school) and psychosocial correlates (meaning in life, social support, positive and negative affects) of QoL in HIV-infected persons living in Mozambique, a country with a high prevalence of HIV but also with well-structured strategies to fight the disease. To that end, we made correlational analyses followed by regression models and examined potential mediation processes among predictors. All correlates were relevant except for sex. Meaning in life was the strongest predictor, while social support was the weakest. Schooling was both directly and indirectly related with QoL—in the latter case, it was mediated by meaning in life, social support and positive affect. Our findings suggest that investments in education may be highly rewarding to Mozambicans, and that satisfying needs for self-actualization and purpose may be more urgent than improving social connections.