Intense exercise decreases the cerebral metabolic ratio of O2 to carbohydrates (glucose +½ lactate) and the cerebral lactate uptake depends on its arterial concentration, but whether these variables are influenced by O2 availability is not known. In six males, maximal ergometer rowing increased the arterial lactate to 21.4 ± 0.8 mm (mean ±s.e.m.) and arterial–jugular venous (a–v) difference from −0.03 ± 0.01 mm at rest to 2.52 ± 0.03 mm (P < 0.05). Arterial glucose was raised to 8.5 ± 0.5 mm and its a–v difference increased from 1.03 ± 0.01 to 1.86 ± 0.02 mm (P < 0.05) in the immediate recovery. During exercise, the cerebral metabolic ratio decreased from 5.67 ± 0.52 at rest to 1.70 ± 0.23 (P < 0.05) and remained low in the early recovery. Arterial haemoglobin O2 saturation was 92.5 ± 0.2% during exercise with room air, and it reached 87.6 ± 1.0% and 98.9 ± 0.2% during exercise with an inspired O2 fraction of 0.17 and 0.30, respectively. Whilst the increase in a–v lactate difference was attenuated by manipulation of cerebral O2 availability, the cerebral metabolic ratio was not affected significantly. During maximal rowing, the cerebral metabolic ratio reaches the lowest value with no effect by a moderate change in the arterial O2 content. These findings suggest that intense whole body exercise is associated with marked imbalance in the cerebral metabolic substrate preferences independent of oxygen availability.