We aimed to determine whether the quality of life (QOL) in the patients infected with human immunodeficiency virus (HIV) infection was influenced by satisfaction with social support, coping style and hopelessness. One hundred and thirty-eight HIV-infected patients were prospectively studied in this multicentre, longitudinal study. The QOL was assessed by Medical Outcome Study Health Survey SF-36, social support by Sarason Social Support Questionnaire, hopelessness by Beck Hopelessness Scale, and coping by Billing and Moos Inventory of coping with illness. The QOL did not correlate with age, sex, race, HIV risk factor, education or marital status. Employment (P = 0.0001), higher income (P = 0.03), satisfaction with social support (P = 0.04), regardless of the source of that support, and problem-focused coping (P = 0.03) were associated with a significantly better QOL, while, emotion-focused coping (r = -0.19, P = 0.04), avoidant coping (r = 0.40, P = 0.0001), hopelessness (r = -0.64, P = 0.0001) and AIDS (P = 0.09) were predictors of poorer QOL. Physical functioning correlated positively with employment (P = 0.0001), and inversely with AIDS (P = 0.0002), hopelessness (P = 0.03), avoidant coping (P = 0.03), and age (P = 0.10). At 6 months follow up, QOL score had changed in 20% of the patients; older age (P = 0.01), and lesser satisfaction with social support (P = 0.15) were associated with a decline in QOL, while adherence with antiretroviral therapy (P = 0.006) was associated with an increase in QOL score. Seven of 138 patients died during follow up; these patients had significantly lower QOL at baseline than all other patients (P = 0.003). Interventions to alleviate hopelessness, maladaptive coping, and enhancement of satisfaction with social support may improve overall QOL in HIV-infected patients. Older patients with HIV were less satisfied with their social support, were more likely to utilize unhealthy coping styles, and experienced a greater decline in QOL over time.