Sleep deprivation and/or a high workload situation can adversely affect driving performance, decreasing a driver's capacity to respond effectively in dangerous situations. In this context, to provide useful feedback and alert signals in real time to the drivers physiological and brain activities have been increasingly investigated in literature. In this study, we analyze the increase of cerebral workload and the insurgence of drowsiness during car driving in a simulated environment by using high resolution electroencephalographic techniques (EEG) as well as neurophysiologic variables such as heart rate (HR) and eye blinks rate (EBR). The simulated drive tasks were modulated with five levels of increasing difficulty. A workload index was then generated by using the EEG signals and the related HR and EBR signals. Results suggest that the derived workload index is sensitive to the mental efforts of the driver during the different drive tasks performed. Such workload index was based on the estimation the variation of EEG power spectra in the theta band over prefrontal cortical areas and the variation of the EEG power spectra over the parietal cortical areas in alpha band. In addition, results suggested as HR increases during the execution of the difficult driving tasks while instead it decreases at the insurgence of the drowsiness. Finally, the results obtained showed as the EBR variable increases of its values when the insurgence of drowsiness in the driver occurs. The proposed workload index could be then used in a near future to assess on-line the mental state of the driver during a drive task.