Although the relationship between self-efficacy and health-related behaviors is well known, limited data are available describing the association between self-efficacy and HIV stigma. Specifically, it is not known if the relationship between self-efficacy and health outcomes is mediated by HIV stigma. This study aimed to test these relationships. Data were collected from 202 HIV/AIDS patients in China using questionnaires measuring self-efficacy for disease management, self-reported 7 day medication adherence, perceived HIV/AIDS stigma and quality of life. The total mean score for self-efficacy was 6.73 (range, 2.78-10.0), and the total mean score for HIV stigma was 102.24 (range, 57.0-148.0). Seventy-four percent (150/202) of subjects reported missing no medication doses during past 7 days, and 73% (148/202) subjects reported a quality of life score over 60. There was a moderate level of association between self-efficacy and HIV stigma (Pearson r=-0.43, p=0.000). High self-efficacy predicted better medication adherence (odds ratio [OR]=1.82, 95% confidence interval [CI]=1.40-2.36) and better quality of life (OR=1.28, 95% CI=1.03-1.60) after controlling for demographic and HIV related characteristics. HIV stigma partially mediated the relationship between self-efficacy and medication adherence (OR=1.64, 95% CI=1.26-2.15; Sobel test result Z=1.975, p=0.048). HIV stigma totally mediated the relationship between self-efficacy and quality of life (OR=1.15, 95% CI=0.91-1.46; Sobel test result Z=2.362, p=0.018). The results suggest that, although self-efficacy is an important predictor for medication adherence and quality of life, HIV stigma as a mediator should not be neglected. Health care providers should also evaluate HIV stigma conditions when seeking to improve self-efficacy through interventions.