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African immigrants living in the United States are disproportionately and uniquely affected by HIV. Evidence shows that stigma may contribute to this inequity. Applying a biopsychosocial model of health, our qualitative study explored HIV-related stigma and its impact on African immigrants living with HIV in a large northwestern U.S. metropolitan area. We conducted in-depth, semi-structured interviews with 20 African immigrants living with HIV. In the biological health realm, HIV-related stigma contributed to adverse health care environments, disruptions in care, and poor physical health. In the psychological health realm, it was associated with emotional vulnerability, depressive symptoms, and negative coping. In the social health realm, stigma lead to disclosure challenges, isolation, and poor social support. HIV-related stigma was an extensive and pervasive burden for this population. The biopsychosocial model was a helpful lens through which to explore HIV-related stigma and identify opportunities for future research and intervention.