This study investigated the relationship between life satisfaction, self-esteem, and perceived health for an ethnically diverse, low SES sample of primary care patients. Results indicated that several specific domains of health-related quality of life (HRQL), including health perception, social functioning, mental health, and energy/fatigue, significantly predicted life satisfaction in this sample of 60 patients. Self-esteem mediated this relationship, partially with health perception and fully with the remaining three domains. The results of this study underscore the importance of healthcare interventions that consider the bidirectional relationship between physical and emotional well-being.