The Perceived Deficits Questionnaire (PDQ) is a part of the Multiple Sclerosis (MS) Quality of Life Inventory that assesses self-perceived cognitive difficulties. We used baseline data from 49 MS subjects participating in a clinical trial to evaluate the correlation of the PDQ with two measures of cognitive impairment, the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test, 2nd edition (CVLT-II), total score, and one measure of depression, the Beck Depression Inventory-Amended (BDI-IA). The PDQ correlated significantly (r = 0.42; 95% confidence interval [CI], 0.15 to 0.62; p = 0.003) with the BDI-IA scores but not with either the PASAT (r = -0.22; 95% CI, -0.48 to 0.06; p = 0.2) or the CVLT-II total (r = -0.17; 95% CI, -0.43 to 0.12; p = 0.25). A subset of 38 of these subjects who scored worse than 0.5 standard deviation below the mean on the PASAT or CVLT-II received a more extensive neuropsychological battery of tests. No significant correlations were found between any of these tests and the PDQ. These results suggest that self-perceived cognitive dysfunction relates more to depression than to objective cognitive dysfunction.