BACKGROUND Human immunodeficiency virus (HIV) infection has become a serious health problem for low-income African American women in their childbearing years. Interventions that help them cope with feelings about having HIV and increase their understanding of HIV as a chronic disease in which self-care practices, regular health visits, and medications can improve the quality of life can lead to better health outcomes. OBJECTIVE This study aimed to determine the efficacy of an HIV self-care symptom management intervention for emotional distress and perceptions of health among low-income African American mothers with HIV. METHOD Women caregivers of young children were randomly assigned to self-care symptom management intervention or usual care. The intervention, based on a conceptual model related to HIV in African American women, involved six home visits by registered nurses. A baseline pretest and two posttests were conducted with the mothers in both groups. Emotional distress was assessed as depressive symptoms, affective state, stigma, and worry about HIV. Health, self-reported by the mothers, included the number of infections and aspects of health-related quality of life (i.e., perception of health, physical function, energy, health distress, and role function). RESULTS Regarding emotional distress, the mothers in the experimental group reported fewer feelings of stigma than the mothers in the control group. Outcome assessments of health indicated that the mothers in the experimental group reported higher physical function scores than the control mothers. Within group analysis over time showed a reduction in negative affective state (depression/dejection and tension/anxiety) and stigma as well as infections in the intervention group mothers, whereas a decline in physical and role function was found in the control group. CONCLUSIONS The HIV symptom management intervention has potential as a case management or clinical intervention model for use by public health nurses visiting the home or by advanced practice nurses who see HIV-infected women in primary care or specialty clinics.