ABSTRACT Background Research related to HIV stigma is in its initial stages in Pakistan. With the recent increase in HIV cases among injection drug users, there is a growing need to study the psychosocial aspects of the disease to address and mitigate the factors associated with stigma. HIV stigma has been identified as a contributor to depression and a barrier to effective treatment. Aim This study examines the moderating role of perceived social support from three sources, i.e., family, friends, and significant others, in reducing the impact of HIV stigma on depression among individuals living with HIV in Pakistan. Methodology 150 male HIV patients were approached whose likely mode of infection was through injection drug usage. The study explored the moderating role of three sources of perceived social support. Semi-structured interviews and standardized measurements were employed to assess levels of stigma, depression, and perceived social support. Results The findings indicated that family support emerged as the most effective moderating factor in the relationship between HIV/AIDS stigma and depression. Support from significant others was observed as the second one. However, the study did not find substantial moderating effects from friends’ support on the relationship between stigma and depression. Conclusion In Pakistan, where a collectivist societal structure prevails, interventions to reduce HIV/AIDS stigma should focus on strengthening the family support system for patients. The study’s outcomes underscore the importance of tailored interventions that consider the cultural context to mitigate the adverse impact of HIV stigma on mental health of people living with HIV.