Objectives: (1) To examine the relationship between subjective, physical, and mental fatigue, depression, and endocrine abnormalities in outpatients who had sustained traumatic brain injury (TBI). (2) To explore the interrelationship between these factors and community integration. Hypotheses: (1) There is a correlation between endocrine abnormalities and subjective reporting of fatigue and depression. (2) There is a correlation between endocrine abnormalities and objective measures of both physical fatigue and mental vigilance. (3) There is a correlation between endocrine abnormalities and community integration. Participants: Twenty-one TBI patients, with a definitive diagnosis of moderate to severe TBI with an onset at least 3 months prior to enrollment based on the 24-hour Glasgow Coma Scale, aged 18 to 55 years. Methods: Subjects' depression, fatigue, community integration, and quality of life were assessed subjectively using several validated metrics. Mental vigilance was evaluated using the Digit Vigilance Task (DVT) while physical fatigue was measured using a timed wall-sit task. A comprehensive endocrine evaluation was performed simultaneously and the available data were evaluated for correlations. Results: Lower levels of IGF-1 were related to an increase in subjective reporting of fatigue (P = .002) and depression (P = .01) after TBI, while higher levels of IGF-1 levels were related to greater community integration (P = .025), and 9 AM cortisol levels were associated with greater fatigue (P = .003). No correlation between any hormonal levels and the DVT (P = .25) and timed wall-sit (P = .49) could be identified. Conclusions: The data suggest a possible relationship between endocrine dysfunction and the subjective reporting of fatigue after TBI, not found with the objective measures. This may be because many of the participants were unable to complete these tasks. Further investigation with improved objective metrics is required to address the potential for the development of treatment related strategies.