Self-report health status measures are consistently associated with medical outcomes and are cost-effective. Studies using such measures find that those who live in rural areas or have limited access to support experience poorer health status and poorer outcomes. A survey addressing these issues was administered to 401 HIV-positive persons throughout Alabama. Hierarchical regression models examined the relation of housing stability, stress, substance use and other variables to physical (PCS) and mental (MCS) health status. The sample was 34% female and 66% African-American. Most were receiving antiretroviral medications, and nearly 20% were in unstable housing. Age showed a significant negative relationship to health status. CD4 cell count (p < 0.01) was positively associated with PCS; perceived general stress (p < 0.02) and housing stability (p < 0.04) were negatively associated. The model accounted for 14% of the variance in PCS (p < 0.001). For MCS, general stress (p < 0.001) was negatively associated and substance use tended towards a negative association (p < 0.075). Social support (p < 0.02) was positively associated with MCS. The model accounted for nearly 31% of the MCS variance (p < 0.001). Health status among HIV-positive persons may be improved by assessing and addressing social issues such as social isolation, life stressors and housing.