In this study, we assessed the relationship between brain estimated specific gravity (eSG) and clinical symptoms, therapeutic intensity level, and outcome in human traumatic brain injury (TBI). Brain weight, volume, and eSG of the noncontused hemispheric areas were measured from computed tomography (CT) DICOM images on the initial (5 ± 6 h) CT of 120 patients with severe TBI. Control values were obtained from 40 healthy patients. The eSG of the noncontused hemispheric areas was significantly higher in TBI patients than in controls. eSG was higher in patients having a Marshall CT classification of 3 or 4 or a low initial Glasgow coma score. Two groups were defined according to the eSG of the noncontused hemispheric areas: less than (n = 83, 69%) or more than (n = 37, 31%) the threshold of normality (defined as 1.96 sd above normal = 1.0355 g/mL). The occurrence of mydriasis, use of osmotherapy at the scene of the accident, and therapeutic intensity level were higher in the increased eSG group. The outcome at intensive care unit discharge was worse in patients with an increased eSG although the difference was no longer significant at 1 yr. eSG determination by CT analysis might be relevant in the early management of TBI.