Driving tasks are vulnerable to the effects of sleep deprivation and mental fatigue, diminishing driver's ability to respond effectively to unusual or emergent situations. Physiological and brain activity analysis could help to understand how to provide useful feedback and alert signals to the drivers for avoiding car accidents. In this study we analyze the insurgence of mental fatigue or drowsiness during car driving in a simulated environment by using high resolution EEG techniques as well as neurophysiologic variables such as heart rate (HR) and eye blinks rate (EBR). Results suggest that it is possible to introduce a EEG-based cerebral workload index that it is sensitive to the mental efforts of the driver during drive tasks of different levels of difficulty. Workload index was based on the estimation of increase of EEG power spectra in the theta band over prefrontal areas and the simultaneous decrease of EEG power spectra over parietal areas in alpha band during difficult drive conditions. Such index could be used in a future to assess on-line the mental state of the driver during the drive task.