This cross-sectional study examined relationships between HIV-related stigma, social support, and depression in a sample of 340 HIV-infected African American women living in rural areas of the Southeastern United States. Three aspects of social support (availability of different types of support, sources of support, and satisfaction with support) and two aspects of HIV-related stigma (perceived stigma and internalized stigma) were measured. Perceived availability of support (p < .0001), sources of support (p = .03), satisfaction with support (p = .003), perceived stigma (p < .0001), and internalized stigma (p < .0001) were all significantly correlated with depression. Social support variables were negatively correlated and stigma variables were positively correlated with depression. HIV-related perceived stigma and internalized stigma were found to mediate the effect of sources of available support on depression. Study findings have implications for designing and implementing interventions to increase social support and decrease HIV-related stigma in order to decrease depression among African American women with HIV disease. © 2010 Association of Nurses in AIDS Care.