In vivo MRI volumetric analysis enables investigators to evaluate the extent of tissue loss following traumatic brain injury (TBI). However, volumetric studies of pediatric TBI are sparse, and there have been no volumetric studies to date in children examining specific subregions of the prefrontal and temporal lobes. In this study, MRI volumetry was used to evaluate brain volume differences in the whole brain, and prefrontal, temporal, and posterior regions of children following moderate to severe TBI as compared to uninjured children of similar age and demographic characteristics. The TBI group had significantly reduced whole brain, and prefrontal and temporal regional tissue volumes as well as increased cerebrospinal fluid (CSF). Confidence interval testing further revealed group differences on gray matter (GM) and white matter (WM) in the superior medial and ventromedial prefrontal regions, WM in the lateral frontal region, and GM, WM, and CSF in the temporal region. Whole brain volume and total brain GM were reduced, and total ventricular volume, total CSF volume, and ventricle-to-brain ratio (VBR) were increased in the TBI group. Additional analyses comparing volumetric data from typically developing children and subgroups of TBI patients with and without regional focal lesions suggested that GM loss in the frontal areas was primarily attributable to focal injury, while WM loss in the frontal and temporal lobes was related to both diffuse and focal injury. Finally, volumetric measures of preserved frontotemporal tissue were related to functional recovery as measured by the Glasgow Outcome Scale (adapted for children) with greater tissue preservation predicting better recovery.