Background: Although mental fatigue was well-recognized as one of the long-term consequences following mild traumatic brain injury (MTBI) that required ongoing support, evidences for the optimal management remained inadequate. Aims: To investigate the temporal profile of mental fatigue during the first year after MTBI and examine the impact of perceived social support on the recovery from post-MTBI fatigue. Study Design: Observational case-control study. Methods: This study was conducted among post-MTBI patients admitted to the emergency department in a tertiary-care hospital in Sichuan, China. During four waves of assessments at 1 week, 3, 6 and 12 months, mental fatigue was assessed through Mental Fatigue Scale (MFS) whereas social support was assessed by the Multidimensional Scale of Perceived Social Support (MSPSS).Results: There were 65.1%, 37.1%, 34.8% and 32.5% individuals being identified as those with mental fatigue at 1 week, 3, 6 and 12 months, respectively. The scores of MFS didn't change substantially since 3 months post-injury. Compared to non-fatigued MTBI patients, those with long-lasting post-MTBI fatigue reported extremely lower level of perceived social support. Moreover, improved social support at 1 week was negatively associated with the occurrence of long-lasting fatigue. Conclusion: Sufficient social support could significantly decrease the occurrence of long-lasting mental fatigue among MTBI cases. It seemed of great importance to modify the emphasis of rehabilitation to include assessment and improvement of perceived social support at earlier stages after injury.