Hypovigilance is a challenge present in multiple safety-critical domains. Individuals facing hypovigilance see their cognitive abilities reduced, with inferior decision-making accuracy and longer reaction times. In safety-critical situations, this represents a major contributor to accidents and errors, including among aircraft pilots, drivers, and operators from many command and control domains. Operational organizations should either screen for such a capacity while selecting personnel or try to train this ability in realistic simulations. The evaluation of one’s vigilance level has, however, been a long-lasting challenge in applied research. The goal of the current study is to present the first steps towards developing the ability to collect real-time vigilance neurophysiological measurements in safety-critical domains that could be applicable to adaptive training settings. Participants performed a 1 h driving simulation in a monotonous environment with low traffic and their variation in vigilance was assessed using a set of behavioural (Psychomotor vigilance task [PVT]), self-reported (Karolinska sleepiness scale [KSS] and Stanford sleepiness scale [SSS]) and neurophysiological measures (electroencephalograph [EEG] and eye tracker). Behavioural results from the KSS, SSS and PVT supported how the driving simulation reduced participants’ vigilance levels. The Karolinska Drowsiness Test computed from the EEG alpha and theta power bands was related to eye blinks. Together, these measures point towards neurophysiological signals to track vigilance in real time.