This study was performed to investigate the influence of breathing control on the autonomic cardiac regulation at high altitude in adapted and non-adapted awake subjects. We recorded electrocardiogram and pulse oximetry in 14 short-term acclimatized lowlanders and 14 Himalayan Sherpas during resting conditions at an altitude of 5,050 m. Spectrum analysis was performed on synchronized 15 min periods of R-R intervals and the oxygen saturation of arterial blood (SaO2). Despite mean SaO2 being similar in lowlanders and Himalayan Sherpas [78.5 (SD 7.0)% compared to 79.4 (SD5.8)%, respectively], fluctuations in SaO2 were significantly increased in lowlanders compared to Sherpas, thus indicating an unstable regulation of respiration control in lowlanders. Regression analysis demonstrated a significant relationship between spectrum power of SaO2 and the relative power of R-R intervals in the frequency band between 0.01 and 0.08 Hz in lowlanders, but not in Sherpas. Our results demonstrate differences in respiratory and autonomic cardiac control between non-adapted lowlanders and Himalayan high-altitude residents and indicate that unstable breathing control during chronic hypobaric hypoxia is significantly correlated with the autonomic cardiocirculatory regulation.