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Background: Abnormal interhemispheric synchrony has been described in many clinical compromises in brain function, but its prognostic value in neonatal hypoxic-ischemic encephalopathy (HIE) is unknown. Objectives: The study aimed at describing the frequency of abnormal interhemispheric synchrony in infants with HIE and to explore its prognostic value. The main outcome was survival without major disabilities. Methods: We performed a single-center retrospective cohort study and enrolled 40 neonates with HIE who underwent hypothermia. Results: Abnormal interhemispheric synchrony was observed in 23% of the patients with HIE. Sensitivity and specificity values for predicting survival without major disabilities were 90 and 67% for seizures, 50 and 97% for status epilepticus, 60 and 97% for highly abnormal EEG in the first 48 h, and 80 and 97% for EEG asynchrony, respectively. The prognostic value of asynchrony improved to 100% sensitivity, whereas specificity remained unchanged, when associated with highly abnormal EEG within the first 48 h of life. Conclusions: Abnormal interhemispheric synchrony was observed in a quarter of the patients with HIE. This pilot study suggests that the prognostic value of asynchrony is excellent, especially when combined with EEG background analysis.