OBJECTIVE: To determine whether systemic inflammation-modulating cytokine expression is related to heart rate variability (HRV) in newborns with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: The data from 30 newborns with HIE were analyzed. Cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IL-1beta, TNF-alpha, IFN-lambda) were measured either at 24 h of cooling (n=5), 72 h of cooling (n=4) or at both timepoints (n=21). The following HRV metrics were quantified in the time domain: alpha_S, alpha_L, root mean square (RMS) at short time scales (RMS_S), RMS at long time scales (RMS_L), while low-frequency power (LF) and high-frequency power (HF) were quantified in the frequency domain. The relationships between HRV metrics and cytokines were evaluated using mixed-models. RESULT: IL-6, IL-8, IL-10, and IL-13 levels were inversely related to selected HRV metrics. CONCLUSION: Inflammation-modulating cytokines may be important mediators in the autonomic dysfunction observed in newborns with HIE.