Near infrared spectroscopy (NIRS) was used to asses changes in regional cerebral oxygen saturation (rSO2) in 8 head injured patients with an intracranial pressure (ICP) higher or lower than 25 mmHg (n = 4 for each group). NIRS values in the high ICP group (> 25 mmHg) were significantly lower than in the low ICP group (< 25 mmHg). In contrast, arterial pO2, pCO2, peripheral oxygen saturation and transcranial Doppler sonography (TCD) values were similar in both groups. To further investigate changes in rSO2 to changes in peripheral oxygen saturation and arterial pO2, patients of both groups underwent an artificial hyperoxygenation (50% O2) period of 3 minutes. Both groups revealed similar values in peripheral oxygen saturation, arterial pO2, and TCD velocities at the end of the hyperoxygenation period. However, rSO2 values in patients with an ICP > 25 mmHg were significant lower than in patients with an ICP < 25 mmHg after the hyperoxygenation period. In addition, patients with an ICP < 25 mmHg revealed a significant increase in rSO2 values at the end of the hyperoxygenation period, not detectable in patients with an ICP > 25 mmHg. Our results suggest that NIRS may be an additional diagnostic tool in the non-invasive evaluation of impaired cerebral microcirculation in patients with increased intracranial pressure.