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Fatigue is a complex, multidimensional phenomenon that commonly occurs following traumatic brain injury (TBI). The thalamus—a structure vulnerable to both primary and secondary injuries in TBI—is thought to play a pivotal role in the manifestation of fatigue. We explored how neuroimaging markers of local and global thalamic morphometry relate to the subjective experience of fatigue post-TBI.Sixty-three Veterans with a history of mild TBI underwent structural magnetic resonance imaging and completed questionnaires related to fatigue and psychiatric symptoms. FMRIB's Software (FSL) was utilized to obtain whole brain and thalamic volume estimates, as well as to perform regional thalamic morphometry analyses.Independent of age, sex, intracranial volume, posttraumatic stress disorder, and depressive symptoms, greater levels of self-reported fatigue were significantly associated with decreased right (P = .026) and left (P = .046) thalamic volumes. Regional morphometry analyses revealed that fatigue was significantly associated with reductions in the anterior and dorsomedial aspects of the right thalamic body (P < .05). Similar trends were observed for the left thalamic body (P < .10).Both global and regional thalamic morphometric changes are associated with the subjective experience of fatigue in Veterans with a history of mild TBI. These findings support a theory in which disruption of thalamocorticostriatal circuitry may result in the manifestation of fatigue in individuals with a history of neurotrauma.