The acute metabolic events linked to the evolution of selective axonal pathology in the white matter following diffuse brain injury have not previously been evaluated due to the paucity of relevant experimental models. Here, we utilized a new model of inertial brain injury in the pig that selectively damages axons in the white matter, and applied proton and phosphorous magnetic resonance spectroscopy (MRS) to noninvasively monitor the temporal course of metabolic changes following trauma. Evaluating four pigs with MRS prior to injury, within 1 h and 3 and 7 days postinjury, we found that widespread axonal injury was produced in the absence of changes in pH, PCr/Pi, or the concentrations of ATP, and lactate. However, we did observe an acute 60% loss of intracellular Mg2+ levels, which gradually resolved by 7 days postinjury. In addition, we found that the levels of the neuron marker, N-acetylaspartate (NAA), acutely dropped 20% and remained persistently decreased for at least 7 days postinjury. Moreover, the changes in Mg2+ and NAA were found with MRS in the absence of abnormalities with conventional magnetic resonance imaging (MRI). These results show that (1) profound alterations in intracellular metabolism occur acutely following diffuse axonal pathology in the white matter, but in the absence of indicators of ischemia, and (2) axonal pathology may be evaluated with high sensitivity utilizing noninvasive MRS techniques.