Objective: Differences in the cardiovascular and hypothalamic-pituitary-adrenal (HPA) axis functions at high altitudes (HAs) between visitors to and natives of HA were examined. Methods: The cardiovascular functions and peripheral oxygen saturation (SPO<sub>2</sub>) were monitored, and the cortisol awakening response (CAR) and nighttime cortisol concentration (NCC), as indices of the HPA axis function, were determined in 25 trekkers and 21 Sherpas during an Annapurna circuit trek. Results: SPO<sub>2</sub> decreased less in the Sherpas than in the trekkers at HAs (3,540, 3,800, and 4,800 m). Blood pressure and heart rate in the Sherpas changed concurrently during the trek; however, a tachycardic response occurred without changes in blood pressure in the trekkers at HAs. The CAR and NCC at HAs in the trekkers differed from those observed at 1,100 m and those observed at HAs in the Sherpas. The trekkers exhibited an elevated morning cortisol level at 3,540 and 3,800 m, a heightened CAR at 4,800 m, and an elevated NCC at 3,800 m. Alteration of the CAR resulted in an increase in the integrated volume of cortisol released within the first hour after awakening (CARauc) in the trekkers. The changes in SPO<sub>2</sub> occurred concurrently with the changes in the CARauc and the heart rate in the trekkers. Conclusions: The alterations of CAR occurred at HAs where blood pressure levels reached a peak plateau, which is associated with an increase in heart rate at HAs in the trekkers. The CAR was unaltered in the Sherpas during the trek.