BACKGROUND AND OBJECTIVE: Major deficits in the autonomic nervous system function, detected by measuring heart rate variability (HRV), are reported in neonatal hypoxic-ischemic encephalopathy (HIE)). However, it is unknown if they will recover in the long-term. Because of the possible implications for the neurological outcome, this study aimed to evaluate the HRV at school age, in a cohort of children who survived HIE managed with therapeutic hypothermia. METHODS: A cross-sectional study of HRV in 40 children: 20 HIE survivors and 20 healthy peers. All underwent 5-min plethysmography using the PPG Stress Flow device (BioTekna Italy). Absolute and normalized HRV spectral power in the very low frequency (VLF), low frequency (LF), and high frequency (HF) bands and total power were compared between patients and healthy children. The outcome evaluation included neurological, cognitive (WISC-IV), and psychosocial (Parent Stress Index-Short Form-PSI-SF and psychosocial interview) measures. RESULTS: All mean HRV values were significantly higher in survivors of HIE, compared to healthy peers, with the larger effect size for the HF band (Total Power 8.57 +/- 0.59 vs 7.82 +/- 0.77 ms(2), p .003 ES 0.21; HF 7.82 + 0.77 vs 8.57 + 0.59 ms(2), p .001 EF 0.24). None of the children had major health, neurological and psychosocial (PSI-SF/interview) problems. The IQ (WISC-IV) was normal in 17/20 patients, borderline in 2, and <70 in 1. CONCLUSIONS: HRV measures highlight autonomic dysfunction at school age in survivors of neonatal HIE, in the absence of major neurodevelopmental and psychosocial problems. The significance of this finding for children\'s future life needs further neuropsychiatric investigations and longer follow-up.