Aims: This study aimed to examine the differential treatment effects of cognitive-behavioral therapy (CBT) and supportive psychotherapy (SPT) on self-reported symptoms of depression in individuals with traumatic brain injury (TBI) who sought treatment for major depressive disorder (MDD). Methods: Participants were individuals with a documented TBI meeting criteria for MDD who, as part of a larger randomized controlled trial comparing treatments for MDD after TBI, received CBT (n = 22) or SPT (n = 22). The average age of participants was 48.8 years (standard deviation = 10.2), 57.1% were female, 57.5% were Caucasian, 20% were Hispanic and 15% were African-American. The main outcome measure was the Beck Depression InventoryII (BDI-II). Results: Mean total BDI-II score for all participants combined at baseline was 25 (standard deviation = 10.0). There were no significant differences in total BDI-II score between treatment groups at either baseline or at the end of treatment. Participants treated with CBT reported significant improvements in sadness, loss of interest and loss of interest in sex, while participants treated with SPT reported significant improvements in symptoms of agitation and irritability. Conclusion: SPT may better target symptoms of behavioral disinhibition (agitation and irritability), while CBT may better target mood symptoms (sadness) and their behavioral manifestations (loss of interest and loss of interest in sex).