Evaluating the ecological validity of neuropsychological tests has become an increasingly important topic. Previous research suggests that neuropsychological tests have a moderate level of ecological validity when predicting everyday functioning. The presence of depressive symptoms, however, may impact the relationship between neuropsychological tests and real world performance. The current study empirically tests this hypothesis in a sample of 216 participants with moderate to severe traumatic brain injury (TBI) who completed neuropsychological testing, self-report of mood symptoms, and report of everyday functioning six months post-injury. Contrary to some previous research and clinical lore, results indicated that depression was weakly related to neuropsychological test performance, although it was more strongly related to everyday functioning. Neuropsychological test performance was also significantly related to everyday functioning. The ecological validity of the neuropsychological tests together was not impacted by depressive symptoms, when predicting significant other ratings of functional status. However, patient self-report seems somewhat less related to neuropsychological performance in those with significant depressive symptoms. Neuropsychological test performance was equally related to self and other report of everyday functioning in patients without significant depressive symptoms.