This study examined social support and gender differences as correlates of self-esteem: Implications for improving health among patients living with HIV/AIDS in Ondo State, Nigeria. Using accidental sampling technique, one hundred and ninety-eight patients were tested. The dimensions of social support were measured using scale of Perceived Social Support Assessment and self-esteem was measured using the Rosenberg Self-Esteem Scale. In order to determine the extent and direction of associations among the study variables, Pearson Product Moment Correlation (PPMC) analysis was conducted. Multiple Regression analysis was then used to test hypothesis 1, 2, and 3. The study revealed that social support had a significant positive relationship with self-esteem The result indicated that gender significantly predicted influence on self-esteem [β = .23; t = .27; p > 0.05]. The result also revealed that social support significantly predicted self-esteem [β = .31; t = .27; p > 0.05]. On the contribution of all the independent variables (gender differences and social support) to the prediction of self-esteem, the outcome of the summary in Table 4.2 signify that all the independent variables when pulled together yield a multiple R of .21 and R2 of .045 [ F (2, 198) = 18.19*, p < 0.01]. Based on the result of the study, it was recommended that government organizations, non-governmental organization, religious organization and communities should all take part in giving the PLWH a holistic support and encouragement needed pending the time they spend in recovery until they begin full adult functional life.