This study delineates gender differences in psychological well-being for rural men and women living with HIV/AIDS. The Chronic Illness Quality of Life Model (CIQOL) (Heckman, 2003) serves as the conceptual framework. All participants were recruited through ASOs in 13 U.S states. Analyses examining interactions among variables found that women who reported higher levels of physical compromise reported significantly greater perceptions of loneliness compared to women who reported less physical compromise. Loneliness in males did not vary by level of physical compromise. The study results suggest that AIDS mental health interventions are needed for rural women. HIV-infected rural women appear to engage frequently in avoidance coping and are vulnerable to increased loneliness if they are experiencing more severe HIV symptomatology.