Abstract. BACKGROUND: In neonatal hypoxic ischemic encephalopathy (HIE), hypo- and hyperglycemia have been associated with poor outcomes. However, glucose variability has not been reported in this population. OBJECTIVE: To examine the association between serum glucose variability within the first 24 hours and two-year neurodevelopmental outcomes in neonates cooled for HIE. STUDY DESIGN: In this retrospective cohort study, glucose, clinical and demographic data were documented from 23 term newborns treated with whole body therapeutic hypothermia. Severe neurodevelopmental outcomes from planned two-year assessments were defined as the presence of any one of the following: Gross Motor Function Classification System levels 3 to 5, Bayley III Motor Standard Score <70, Bayley III Language Score <70 and Bayley III Cognitive Standard Score <70. RESULTS: The neurodevelopmental outcomes from 8 of 23 patients were considered severe, and this group demonstrated a significant increase of mean absolute glucose (MAG) change (–0.28 to –0.03, 95% CI, p = 0.032). There were no significant differences between outcome groups with regards to number of patients with hyperglycemic means, one or multiple hypo- or hyperglycemic measurement(s). There were also no differences between both groups with mean glucose, although mean glucose standard deviation was approaching significance. CONCLUSIONS: Poor neurodevelopmental outcomes in whole body cooled HIE neonates are significantly associated with MAG changes. This information may be relevant for prognostication and potential management strategies.