BACKGROUND Classic teaching suggests that diminished availability of oxygen leads to increased tissue oxygen extraction yet evidence to support this notion in the context of hypoxaemia, as opposed to anaemia or cardiac failure, is limited. METHODS At 75 m above sea level, and after 7-8 days of acclimatization to 4559 m, systemic oxygen extraction [C(a-v)O2] was calculated in five participants at rest and at peak exercise. Absolute [C(a-v)O2] was calculated by subtracting central venous oxygen content (CcvO2) from arterial oxygen content [Formula: see text] in blood sampled from central venous and peripheral arterial catheters, respectively. Oxygen uptake [Formula: see text] was determined from expired gas analysis during exercise. RESULTS Ascent to altitude resulted in significant hypoxaemia; median (range) [Formula: see text] 87.1 (82.5-90.7)% and [Formula: see text] 6.6 (5.7-6.8) kPa. While absolute C(a-v)O2 was reduced at maximum exercise at 4559 m [83.9 (67.5-120.9) ml litre(-1) vs 99.6 (88.0-151.3) ml litre(-1) at 75 m, P=0.043], there was no change in oxygen extraction ratio (OER) [C(a-v)O2/CaO2] between the two altitudes [0.52 (0.48-0.71) at 4559 m and 0.53 (0.49-0.73) at 75 m, P=0.500]. Comparison of C(a-v)O2 at peak [Formula: see text] at 4559 m and the equivalent [Formula: see text] at sea level for each participant also revealed no significant difference [83.9 (67.5-120.9) ml litre(1) vs 81.2 (73.0-120.7) ml litre(-1), respectively, P=0.225]. CONCLUSIONS In acclimatized individuals at 4559 m, there was a decline in maximum absolute C(a-v)O2 during exercise but no alteration in OER calculated using central venous oxygen measurements. This suggests that oxygen extraction may have become limited after exposure to 7-8 days of hypoxaemia.