The objective of the present study is to assess the cerebral saturation under driver fatigue based on the near infrared spectroscopy (NIRS) signals. Twenty healthy male subjects were randomly divided into two groups: A-group (study group) and B-group (control group). All subjects were required to be well rested before the experiment. In A-group the subjects were required to perform the simulated driving task for 3 hours. Cerebral oxygenation signal was monitored for 20 minutes prior to and after the prescribed task period from the left frontal lobe. The results show that cerebral oxygen saturation was found to be significantly lower following 3-hour driving in the task group compared to that in the control group (F = 15.92, p < 0.001). Also a significant difference in selective reaction time was observed between the task group and control group during the post task period (p = 0.021). These findings showed that the cerebral blood oxygen saturation was closely related to the driver fatigue. The decline of the cerebral oxygen saturation might indicate a reduced cerebral oxygen delivery. This suggests that NIRS could provide a non-invasive method to detect driver fatigue.