This study aimed to examine the influence of social support (from personal networks and health care providers) and social undermining (from personal networks) on health-related quality of life (HRQOL; general health perceptions, physical functioning, and depression). Specifically, the authors aimed to identify the nature of the effects (direct, mediating, or moderating) of social support and social undermining on HRQOL. A total of 344 people living with HIV/AIDS and who were patients in a federally funded clinic in New Mexico completed a self-report survey questionnaire. The major findings of this study are the following: (a) social support and social undermining had direct and indirect effects on HRQOL—there was no evidence of a moderating effect of social support and social undermining; (b) for direct effects, social undermining was a stronger predictor of HRQOL than social support with social support variables having positive relations and social undermining variables having negative relations with HRQOL; and (c) for indirect effects, providers' social support partially mediated the influence of unstable employment/unemployment and social undermining on HRQOL.