The authors examined the contribution of working memory performance to subjective cognitive complaints in HIV infection beyond the influence of depressive symptoms. Thirty-six adults with HIV infection were administered neuropsychological (NP) tests of working memory, complex psychomotor efficiency, verbal learning, delayed recall, and questionnaires measuring depressive symptoms and cognitive complaints. Working memory performance, depression scores, and complex psychomotor efficiency were most strongly associated with self-reported cognitive complaints, whereas verbal learning scores and simple psychomotor efficiency showed more modest associations. Regression analyses revealed working memory performance to be the strongest NP predictor of self-reported cognitive complaints, comparable with depression scores in the amount of variance explained. These results suggest that working memory performance may be well suited to reflect how patients function in their everyday environment.