Twenty-six infants with hypoxic-ischemic encephalopathy (HIE) were randomized to normothermia or to systemic hypothermia. The hypothermia group had less cortical gray matter signal abnormality on magnetic resonance imaging (MRI) (1/12 vs 7/14 infants in the normothermic group; P = .036), which may indicate differing regional benefit from systemic hypothermia.