Objective: To examine the relationship between self-reported depression and cognitive functioning in individuals with traumatic brain injury (TBI). Design: Observational; Cross-sectional. Setting: Research center at an urban medical center. Participants: Forty individuals with mild TBI, 90 individuals with moderate/severe TBI and 53 controls enrolled between November 2002 and June 2007. Interventions: None. Main Outcome Measures: Cognitive functioning was measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB). Depression was measured by The Beck Depression Inventory – II (BDI-II). Results: Partial correlation analyses controlling for age, race and education were used to examine the relationship between scores on CANTAB indices derived from a factor analysis (accuracy, speed, executive functioning) and BDI-II scales (total, affective, somatic). Forty-four percent of the mild TBI group, 54% of the moderate/severe TBI group and 14% of the control group were found to be clinically depressed. BDI-II affective subscale scores were negatively correlated with speed index scores in the moderate/severe TBI (r=−.35, P=.01) such that greater depression was associated with slower speed. Surprisingly, in the control group this relationship was reversed (r=.32, P=.04). None of the other cognitive indices were significantly related to depression. Conclusions: There was little overall relationship between cognition and depression in individuals with TBI and nondisabled controls as measured by the CANTAB and BDI-II. Affective symptoms of depression may be more closely related to cognitive difficulties than somatic symptoms in individuals with moderate-severe TBI.