The primary aim of this study was to examine the complex relationship between multiple levels of stressors and health-related quality of life among residents of low-income neighborhoods in Francistown, Botswana. Using a cross-sectional quantitative design (both descriptive and explanatory) and using primarily close-ended interviews with a random sample of 388 residents, this study examined the role of individual life stressors, stressful life events, chronic life stressors, and family economic pressure on overall health status quality of life) and the physical, psychological and level of independence domains of health. The major hypothesis of the study was that individual life stressors and community-level stressors would negatively influence health-related quality of life and that social support and social capital would moderate these relationships