OBJECTIVE: Central topography of autonomic nervous system (ANS) function has yet to be fully deciphered. In adults it has been shown to lateralize sympathetic and parasympathetic influence predominantly to the right and left cerebral hemispheres, respectively. We examined functional topography of central ANS in newborn subjects utilizing spectral analysis of heart rate variability (HRV), an established measure of ANS function. STUDY DESIGN: We studied newborns with hypoxic-ischemic encephalopathy participating in a prospective study undergoing a therapeutic hypothermia protocol.We included subjects with continuous heart rate data over the first 3 h of normothermia (post rewarming) and brain magnetic resonance imaging, which was reviewed and scored according to a 4 region scheme. HRV was evaluated by spectral analysis in the low-frequency (0.05 to 0.25 Hz) and high-frequency (0.3 to 1 Hz) ranges. The relationship between injured brain regions and HRV was studied using multiple regressions. RESULTS: Forty eight newborns were included. When examined in isolation, right hemisphere injury had a significant negative effect on HRV (-0.088; 95% CI: -0.225,-0.008). The combination of posterior fossa region injury with right hemispheric injury or left hemispheric injury demonstrated significant positive (0.299; 95% CI: 0.065, 0.518) and negative (-0.475; 95% CI: -0.852, -0.128) influences on HRV, respectively. The association between brain injury location and HRV in the high-frequency range did not reach significance. CONCLUSION: Our data support the notion that lateralized cerebral modulation of the ANS, specifically of its sympathetic component, is present in the term newborn, and suggest complex modulation of these tracts by components of the posterior fossa.