This study investigates the relationship of three protective factors: self transcendence, social interest, and spirituality to well-being among adults living with HIV or AIDS. It is the first study to explore the relationships of these protective factors to well-being. A convenience sample of 115 adults living with HIV or AIDS completed the Self-Transcendence Scale, the Social Interest Index- Short Form-Revised, the Spiritual Perspective Scale, and the Index of Well-Being. The participants were adults diagnosed with HIV or AIDS residing in a large southeastern U.S. city. Data were analyzed with correlational and multiple regression methods. Statistically significant positive moderate to strong relationships were found between well-being and self transcendence (r=.66, p<.001), social interest ( r=.51, p<.001), and spirituality (r=.39, p<.001). A stepwise regression demonstrated that self transcendence held the highest variance on well-being among the three protective factors (43%). Additionally, Self transcendence and social interest accounted for 45% of the variance in well-being. In short, the hypothesized positive relationship among these protective factors with well-being was supported. This study provides theoretical and empirical support for linking self transcendence, social interest, and spirituality to well-being among adults living with HIV or AIDS. The clinical implications of these findings are also discussed.