Compensation for hypobaric hypoxia at altitude through increased blood flow and delivery of oxygen is a recognised phenomenon^(1-2); however, its relationship to acute mountain sickness is not yet understood. We measured arterial blood saturation (S_a,O2) and heart rate (HR), at rest and separately during two minutes exercise, by pulse-oximetry in eight subjects, normally resident at sea level, during a 28-day expedition in the Peruvian Andes at altitudes ranging from 3324-5176m (55-68 kPa). We assessed acute mountain sickness using the Lake Louise Consensus scoring system⁽³⁾. Data were collected twice daily on most days of the expedition. In all but one subject, a significant inverse relationship (p=≤0.01) was observed between all the resting HR (HRrest) and resting S_a,O2 (S_a,O2rest) values for each individual subject. Despite that, daily estimates of a surrogate for resting oxygen delivery (HRrest x S_a,O2rest) remained within a narrow, near constant, range. Mean values were calculated for S_a,O2rest, HRrest and acute mountain sickness score for the whole trip for each subject. The mean S_a,O2rest values varied from 81.3% to 93.2%. The mean HRrest also varied considerably, from 70 bpm to 106 bpm, with the coefficients of variation inversely related to S_a,O2rest values (r=0.795, p=0.032). Mean acute mountain sickness scores were significantly related to S_a,O2rest values in all but one subject (r=0.926, p=0.002). The outlier attended the expedition only for 20 days and did not undertake the exercise study. Mean individual S_a,O2 values for exercise (S_a,O2Ex) correlated with, but were significantly lower than S_a,O2rest (S_a,O2Ex = 1.3363 x S_a,O2rest – 33.734, r=0.975, p<0.001). The mean acute mountain sickness scores correlated with S_a,O2Ex (r=0.917, p=0.003). Acute mountain sickness appears to be related to S_a,O2, which, in turn, indicates (inversely) the degree of respiratory compensation for ambient hypoxia. HR variation, here, suggests cardiac output compensation; such compensation appeared more pronounced in those subjects with lower S_a,O2.