We measured simultaneous changes in jugular venous oxygen saturation, brain tissue oxygen tension, and cerebral tissue oxygen index by using near-infrared spectroscopy during normobaric hyperoxygenation in eight severely brain-injured patients. Patients were ventilated at their baseline fraction of inspired oxygen (FIO(2)), followed by stepped changes in FIO(2) to 1.0, 0.6, and 0.02-0.05 less than baseline. There was an increase (P < 0.01) in jugular venous saturation (mean +/- SD) from a baseline value of 79% +/- 7% to 89% +/- 6% and 84% +/- 8% at an FIO(2) of 1.0 and 0.6, respectively. The changes in brain tissue oxygen tension were from a baseline of 30 +/- 5 mm Hg to 147 +/- 36 mm Hg and 63 +/- 6 mm Hg at an FIO(2) of 1.0 and 0.6, respectively (P < 0.01). The baseline tissue oxygen index was 78% +/- 3%, and this increased to 83% +/- 5% and 80% +/- 4% at an FIO(2) of 1.0 and 0.6, respectively. There was a reduction (P < 0.05) in tissue oxygen index to 76.2% +/- 3.0% when the FIO(2) was reduced to less than baseline. The changes in the three variables followed similar patterns but varied in their degree and speed of response. During brain injury, FIO(2) affects measured variables of cerebral oxygenation.