Long-duration Antarctic expeditions are characterized by isolation, confinement, and extreme environments. Here we describe the time course of cardiac autonomic modulation assessed by heart rate variability (HRV) during 14-month expeditions at the German Neumayer III station in Antarctica. Heart rate recordings were acquired in supine position in the morning at rest once before the expedition (baseline) and monthly during the expedition from February to October. The total set comprised twenty-five healthy crewmembers (n = 15 men, 38 ± 6 yrs, n = 10 women, 32 ± 6 yrs, mean ± SD). High frequency (HF) power and the ratio of low to high frequency power (LF/HF) were used as indices of vagal modulation and sympathovagal balance. HF power adjusted for baseline differences decreased significantly during the expedition, indicating a gradual reduction in vagal tone. LF/HF powers ratio progressively shifted toward a sympathetic predominance reaching statistical significance in the final trimester (August to October) relative to the first trimester (February to April). This effect was particularly pronounced in women. The depression of cardio-vagal tone and the shift toward a sympathetic predominance observed throughout the overwintering suggest a long-term cardiac autonomic modulation in response to isolation and confinement during Antartic overwintering.