STUDY OBJECTIVES: Nocturnal cardiovascular events are more frequent at the beginning and end of the night. It was proposed that this pattern reflects the nocturnal distribution of sleep and sleep stages. Using heart rate variability (HRV), we recently showed an interaction between the circadian system and vigilance states on the regulation of cardiac rhythmicity. Here, we further investigate this interaction in order to clarify the specific effects of sleep stages on the regulation of the heart. DESIGN: Participants underwent a 72-h ultradian sleep-wake cycle procedure in time isolation consisting of alternating 60-min wake episodes in dim light and 60-min nap opportunities in total darkness. SETTING: Time isolation suite. PATIENTS OR PARTICIPANTS: Fifteen healthy young participants; two were subsequently excluded. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The current study revealed that sleep onset and progression to deeper sleep stages was associated with a shift toward greater parasympathetic modulation, whereas rapid eye movement (REM) sleep was associated with a shift toward greater sympathetic modulation. We found a circadian rhythm of heart rate (HR) and high-frequency power during wakefulness and all non-REM sleep stages. A significant circadian rhythm of HR and sympathovagal balance of the heart was also observed during REM sleep. During slow wave sleep, maximal parasympathetic modulation was observed at approximately 02:00, whereas during REM sleep, maximal sympathetic modulation occurred in the early morning. CONCLUSION: The circadian and sleep stage-specific effects on heart rate variability are clinically relevant and contribute to the understanding of the degree of cardiovascular vulnerability during sleep.