People living with HIV/AIDS (PLHA) face several challenges in terms of the medical management of their disease. Alongside this are stigma, discrimination and psychosocial issues associated with HIV infection. In this study, the relationships associated with HIV-related stigma, mental health and quality of life for HIV-positive patients were investigated. This cross-sectional study examined a sample of 450 HIV positive patients from the Infectious Diseases and Behavioral Health Clinic of Imam Khomeini Hospital in the city of Tehran, Iran. PLWHA completed Socio-Demographic Characteristics, Berger Scale Stigma (BSS), General Health Questionnaire (GHQ-28), WHO Quality of life-BREF (WHOQOL-BREF) and Philips Social Support Appraisals (SSA). Stigma was significantly correlated with psychological variables, social support, and quality of life. A prevalence of psychiatric disorders was reported by 78.8%. Findings suggested that psychosocial interventions reduce HIV related stigma, address psychological disorders and build social support to improve quality of life for people living with HIV.