INTRODUCTION: This study explored whether post-resuscitation status resembles severe sepsis in terms of autonomic nervous modulation by using heart rate variability (HRV) analysis. METHODS: Successfully resuscitated nontraumatic out-of-hospital cardiac arrest (OHCA) adult patients in an emergency department were prospectively enrolled as the study group. Age- and sex-matched patients with severe sepsis with and without mechanical ventilation were included as positive controls, while sepsis patients and healthy volunteers were included as negative controls. The HRV measures obtained from 10-minute electrocardiogram were compared among 5 groups of subjects. RESULTS: Sixty-four successfully resuscitated OHCA patients were studied. There were no significant differences in all HRV measures (standard deviation of R-R intervals [SD(RR)], coefficient of variation of R-R intervals [CV(RR)], total power [TP], very-low-frequency component [VLF], low-frequency component [LF], high-frequency component [HF], normalized LF [LF%], normalized HF [HF%], and LF/HF) among the successfully resuscitated OHCA patients and severe sepsis patients with and without mechanical ventilation. Also, no significant differences in all HRV measures were found between nonsurvivors of OHCA group and nonsurvivors of severe sepsis group. In the nonsurvivors of OHCA group and severe sepsis group, the LF% and LF/HF were significantly lower, whereas the HF and HF% were significantly higher, as compared with the survivors of these 2 groups. CONCLUSIONS: The autonomic nervous modulation in the initial phase of OHCA patients resembles that of severe sepsis in that both groups of patients have decreased global HRV (TP, SD(RR), and CV(RR)), sympathovagal balance (LF% and LF/HF), and renin-angiotensin-aldosterone modulation (VLF), as compared to healthy subjects.