Driver fatigue is one of the major implications in transportation safety and accounted for up to 40% of road accidents. This study aimed to analyze the EEG alpha power changes in partially sleep-deprived drivers while performing a simulated driving task.Twelve healthy male car drivers participated in an overnight study. Continuous EEG and EOG records were taken during driving on a virtual reality simulator on a monotonous road. Simultaneously, video recordings from the driver face and behavior were performed in lateral and front views and rated by two trained observers. Moreover, the subjective self-assessment of fatigue was implemented in every 10-min interval during the driving using Fatigue Visual Analog Scale (F-VAS). Power spectrum density and fast Fourier transform (FFT) were used to determine the absolute and relative alpha powers in the initial and final 10 minutes of driving.The findings showed a significant increase in the absolute alpha power (P = 0.006) as well as F-VAS scores during the final section of driving (P = 0.001). Meanwhile, video ratings were consistent with subjective self-assessment of fatigue.The increase in alpha power in the final section of driving indicates the decrease in the level of alertness and attention and the onset of fatigue, which was consistent with F-VAS and video ratings. The study suggested that variations in alpha power could be a good indicator for driver mental fatigue, but for using as a countermeasure device needed further investigations.