Societal prejudice against people living with HIV infection is a formidable public health challenge that can negatively impact health and well-being. We recruited a multiethnic sample of 129 gay and bisexual men living with HIV who completed a brief survey; a subset of participants completed semi-structured qualitative interviews to contextualize the data. In bivariate analyses, stigma was positively and significantly correlated with depression (r = .402, p < .001) and negatively correlated with social support (r = −.482, p < .001). Qualitative interview results captured the mental suffering caused by stigma and coping strategies the men had developed. Although some of the coping strategies reduced the likelihood of experiencing acts of stigmatization, they also exacerbated the psychological stress of living with a stigmatized disease and limited the potential for social support. Our results highlight the need to scale up stigma-reduction programs, particularly those that can bolster social support networks.