The aims of this study were to examine differences in self-schemas between persons living with HIV/AIDS with and without depressive symptoms, and the degree to which these self-schemas predict depressive symptoms in this population. Self-schemas are beliefs about oneself and include self-esteem, HIV symptom management self-efficacy, and self-compassion. Beck's cognitive theory of depression guided the analysis of data from a sample of 1766 PLHIV from the USA and Puerto Rico. Sixty-five percent of the sample reported depressive symptoms. These symptoms were significantly (p ≤ 0.05), negatively correlated with age (r = -0.154), education (r = -0.106), work status (r = -0.132), income adequacy (r = -0.204, self-esteem (r = -0.617), HIV symptom self-efficacy (r = - 0.408), and self-kindness (r = - 0.284); they were significantly, positively correlated with gender (female/transgender) (r = 0.061), white or Hispanic race/ethnicity (r = 0.047) and self-judgment (r = 0.600). Fifty-one percent of the variance (F = 177.530 (df = 1524); p < 0.001) in depressive symptoms was predicted by the combination of age, education, work status, income adequacy, self-esteem, HIV symptom self-efficacy, and self-judgment. The strongest predictor of depressive symptoms was self-judgment. Results lend support to Beck's theory that those with negative self-schemas are more vulnerable to depression and suggest that clinicians should evaluate PLHIV for negative self-schemas. Tailored interventions for the treatment of depressive symptoms in PLHIV should be tested and future studies should evaluate whether alterations in negative self-schemas are the mechanism of action of these interventions and establish causality in the treatment of depressive symptoms in PLHIV.