OBJECTIVES: To examine the temporal relation between fatigue, depression, and daytime sleepiness after traumatic brain injury. Fatigue is a frequent and disabling consequence of traumatic brain injury (TBI). However, it is unclear whether fatigue is a primary consequence of the structural brain injury or a secondary consequence of injury-related sequelae such as depression and daytime sleepiness. PARTICIPANTS: Eighty-eight adults with complicated mild-severe TBI (69% male). MAIN MEASURES: Fatigue Severity Scale; depression subscale of the Hospital Anxiety and Depression Scale; Epworth Sleepiness scale at baseline and 6-month follow-up. RESULTS: A cross-lagged path analysis computed within a structural equation modeling framework revealed that fatigue was predictive of depression (beta = .20, P < .05) and sleepiness (beta = .25, P < .05). However, depression and sleepiness did not predict fatigue (P > .05). CONCLUSIONS: The results support the view of fatigue after TBI as "primary fatigue"-that is, a consequence of the structural brain injury rather than a secondary consequence of depression or daytime sleepiness. A rehabilitation approach that assists individuals with brain injury in learning to cope with their neuropsychological and physical limitations in everyday life might attenuate their experience with fatigue.