A precise evaluation of the brain damage in the first days of severe traumatic brain injured (TBI) patients is still uncertain despite numerous available cerebral evaluation methods and imaging. In 5-10% of severe TBI patients, clinicians remain concerned with prolonged coma and long-term marked cognitive impairment unexplained by normal morphological T2 star, flair, and diffusion magnetic resonance imaging (MRI). For this reason, we prospectively assessed the potential value of magnetic resonance spectroscopy (MRS) of the brain stem to evaluate the functionality of the consciousness areas. Forty consecutive patients with severe TBI were included. Single voxel proton MRS of the brain stem and morphological MRI of the whole brain were performed at day 17.5 +/- 6.4. Disability Rating Scale and Glasgow Outcome Scale (GOS) were evaluated at 18 months posttrauma. MRS appeared to be a reliable tool in the exploration of brainstem metabolism in TBI. Three different spectra were observed (normal, cholinergic reaction, or neuronal damage) allowing an evaluation of functional damage. MRS disturbances were not correlated with anatomical MRI lesions suggesting that the two techniques are strongly complementarity. In two GOS 2 vegetative patients with normal morphological MRI, MRS detected severe functional damage of the brainstem (NAA/Cr < 1.50) that was described as "invisible brain stem damage." MRI and MRS taken separately could not distinguish patients GOS 3 (n = 7) from GOS 1-2 (n = 11) and GOS 4-5 (n = 20). However, a principal component analysis of combined MRI and MRS data enabled a clear-cut separation between GOS 1-2, GOS 3, and GOS 4-5 patients with no overlap between groups. This study showed that combined MRI and MRS provide a reliable evaluation of patients presenting in deep coma, specially when there are insufficient MRI lesions of the consciousness pathways to explain their status. In the first few days post-trauma metabolic (brainstem spectroscopy) and morphological (T2 star and Flair) MRI studies can predict the long-term neurological outcome, especially the persistent vegetative states and minimally conscious state.