Cerebral metabolic rate for oxygen (CMRO2) in gray matter (GM) is a sensitive marker for abnormalities in oxidative metabolism. We combined a near-infrared spectroscopy (NIRS) system with 9.4.T MRI to quantify regional CMRO2 in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Increases in CMRO2 were seen in EAE mice and positive inflammation (CFA) controls at day 35 post-induction when compared to naïve controls. In addition, EAE and CFA mice showed increased CMRO2 from day 14 to 35. These data indicate that inflammation alone, not necessarily linked to a white matter autoimmune disease, could cause abnormal CMRO2 in GM.