AIDS stigmas interfere with HIV prevention, diagnosis, and treatment and can become internalized by people living with HIV/AIDS. However, the effects of internalized AIDS stigmas have not been investigated in Africa, home to two-thirds of the more than 40 million people living with AIDS in the world. The current study examined the prevalence of discrimination experiences and internalized stigmas among 420 HIV-positive men and 643 HIV-positive women recruited from AIDS services in Cape Town, South Africa. The anonymous surveys found that 40% of persons with HIV/AIDS had experienced discrimination resulting from having HIV infection and one in five had lost a place to stay or a job because of their HIV status. More than one in three participants indicated feeling dirty, ashamed, or guilty because of their HIV status. A hierarchical regression model that included demographic characteristics, health and treatment status, social support, substance use, and internalized stigma significantly predicted cognitive-affective depression. Internalized stigma accounted for 4.8% of the variance in cognitive-affective depression scores over and above the other variables. These results indicate an urgent need for social reform to reduce AIDS stigmas and the design of interventions to assist people living with HIV/AIDS to adjust and adapt to the social conditions of AIDS in South Africa.