HIV-related stigma negatively affects the lives of persons living with HIV/AIDS (PLWHA). Homeless/unstably housed PLWHA experience myriad challenges and may be particularly vulnerable to the effects of HIV-related stigma. Homeless/unstably housed PLWHA from 3 U.S. cities (N = 637) completed computer-assisted interviews that measured demographics, self-assessed physical and mental health, medical utilization, adherence, HIV disclosure, and risk behaviors. Internal and perceived external HIV stigma were assessed and combined for a total stigma score. Higher levels of stigma were experienced by women, homeless participants, those with a high school education or less, and those more recently diagnosed with HIV. Stigma was strongly associated with poorer self-assessed physical and mental health, and perceived external stigma was associated with recent non-adherence to HIV treatment. Perceived external stigma was associated with decreased HIV disclosure to social network members, and internal stigma was associated with drug use and non-disclosure to sex partners. Interventions are needed to reduce HIV-related stigma and its effects on the health of homeless/unstably housed PLWHA.