Background: Although major depression (MD) is associated with high levels of disability, the relationships between cognitive dysfunction and self-rated disability are poorly understood. This study examined the relationships between self-rated disability in persons with MD and both self-rated and objectively-measured cognitive functioning. Methods: Twenty-one persons with MD and 21 control participants underwent neuropsychological assessment and z-scores representing deviations from control performance were calculated and averaged across the domains of psychomotor speed, initial learning, memory retention and executive function. Self-ratings of cognitive deficits (SRCDs) were reported on a 6-point scale for overall rating of cognitive change, speed of thinking, concentration, and short-term memory. Disability scores for self-rated physical, mental-health and functional (ie. days out of role) disability were computed from the Brief-Disability Questionnaire and the SF-12 'mental component' subscale. Results: Persons with MD had a mean age of 53.9 years (SD = 11.0, 76% female) and had moderate to high depression severity (mean HDRS 21.7, sd = 4.4). As expected, depression severity was a strong predictor of physical (r = 0.7, p < 0.01), mental-health (r = 0.7, p < 0.01) and functional (r = 0.8, p < 0.001) disability on the Brief Disability Questionnaire. Additionally, for physical disability, both overall SRCDs and objectively-measured psychomotor speed continued to be independent significant predictors after controlling for depression severity, uniquely accounting for 13% and 16% of variance respectively. For functional disability scores, objectively-measured memory impairment and overall SRCDs were no longer significant predictors after controlling for depression severity. Conclusion: While depression severity is associated with disability, the contributions of both self-rated and objectively-measured cognitive deficits are substantial and contribute uniquely and differentially to various forms of disability. Efforts directed at reducing cognitive deficits in depression may have the potential to reduce disability.