The hemodynamic and metabolic effects of 90 minutes normobaric hyperoxia were studied in 20 critically ill patients (11 septic, 9 nonseptic) requiring mechanical ventilation with inspired O2 fraction (FIO2) less than 0.40. Thirty minutes after increasing the FIO2 to 1.0, arterial PO2 had increased from about 100 to about 400 mm Hg, and whole body oxygen uptake (VO2) was decreased 10 percent (p less than 0.05) due to an 18 percent decrease in O2 extraction ratio. During the subsequent 60 minutes of hyperoxia, there was no further significant change in VO2. Cardiac index did not change in hyperoxia, but it increased 10 percent (p less than 0.05) in recovery as systemic vascular resistance decreased. VO2 returned to baseline after 30 minutes recovery at original FIO2 due to increased O2 extraction as well as the increased cardiac output. The decrease in VO2 without a decrease in O2 delivery may reflect maldistribution of blood flow and functional O2 shunting to protect tissue from unphysiologically high PO2. While brief oxygenation is advisable before periods of hypoventilation, the present data suggest that hyperoxic ventilation in these patients with already adequate O2 delivery was counterproductive.