Abstract. BACKGROUND: Therapeutic hypothermia (TH) improves survival and neurodevelopmental outcome in neonatal hypoxic ischemic encephalopathy (HIE). Both, hypoglycemia and hyperglycemia are common in infants with HIE. The relationship between hypoglycemia and hyperglycemia, and immediate outcome has not been well described. METHODS: A retrospective analysis of newborn infants with HIE (N = 56) was conducted. Blood glucose concentrations recorded during the first 96 hours were noted. Glucose levels of infants who underwent TH (TH group, N = 20) were compared with those that did not undergo TH (No-TH group, N = 36). The relationship between blood glucose and mortality and/or moderate/severe disability was determined. RESULTS: Mean ± SD blood glucose concentration during the first 24 hours of age was significantly higher in the TH group (148 ± 65 mg/dl), compared with the No-TH group (113 ± 50 mg/dl; p = 0.02), despite a lower glucose infusion rate in the former (4.05 ± 1.77 mg/kg/hr vs. 5.36 ± 2.51 mg/kg/hr; p = 0.04). One hundred percent of infants (n = 9) in the TH group with blood glucose levels >200 mg/dl during the first 24 hours of age died or had moderate/severe disability, compared with 54.5% of those with blood glucose <200 mg/dl in this group (p = 0.03). A similar effect was not present in the No-TH group. CONCLUSION: Hyperglycemia on the first day portends poor outcome in newborn infants undergoing TH for HIE.