Background:Hypothermia is an established therapy in term neonates to reduce death and disability after perinatal asphyxia. Near-infrared spectroscopy-monitored regional cerebral oxygen saturation (rScO 2 ) and amplitude-integrated electroencephalogram (aEEG)-monitored background pattern have been shown to be early predictors of long-term neurodevelopmental outcome. The aim of this study was to investigate the prognostic value of rScO 2 and aEEG for neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia. Methods: In neonates with HIE who were subjected to hypothermia, the aEEG background pattern and rScO 2 were studied prospectively from admission up to 84 h in relation to early magnetic resonance imaging and neurodevelopmental outcome at 18 mo of age. results: Of 39 infants, 12 neonates died because of neurological deterioration. One had an adverse outcome and 26 had a favorable outcome. The rScO 2 was higher in neonates with adverse outcome, although aEEG scores were lower. Positive predictive values at 12, 24, and 36 h of age for adverse outcome ranged from 50 to 67% for rScO 2 and aEEG; negative predictive values ranged from 73 to 96% for rScO 2 and 90 to 100% for aEEG. Combining rScO 2 and aEEG increased positive predictive values (70-91%) and negative predictive values (90-100%). conclusion: During hypothermia, rScO 2 and aEEG measurements are early predictors of long-term outcome after HIE. Combining both parameters further improves early prediction.