Vigilance is a challenging although imperatively necessary ability to maintain attention in many daily life and work activities. The arousal model of vigilance posits that physiological arousal is critical to regulate sustained attention, for which the locus coeruleus-norepinephrine (LC-NE) system would play a major contributing role. Recent research has proposed that transcutaneous auricular vagus nerve stimulation (taVNS) modulates indirect physiological markers of LC-NE activity, although its effects on vigilance have not yet been examined. Aiming to develop a safe and non-invasive procedure to prevent vigilance failures in prolonged tasks, the present study examined the possibility to mitigate vigilance loss by stimulating the LC-NE system via taVNS. Following a pre-registered protocol, 50 participants completed three randomized repeated-sessions in which either active taVNS at individualized intensity, active taVNS at fixed intensity (0.5 mA), or sham taVNS, was delivered while an attentional and vigilance task (i.e., ANTI-Vea) was completed. Before and after the task, saliva samples were collected to analyze indirect markers (i.e., alpha-amylase and cortisol concentrations) of LC-NE activity. Self-reports of feelings associated with stimulation and guessing rate of active/sham conditions supported the efficacy of the single-blind procedure. Contrary to our predictions, the observed vigilance decrement was not modulated by active taVNS. We discuss the role of changes in alpha-amylase and cortisol concentrations in the vigilance decrement and their validity as indirect markers of LC-NE activity. We highlight the relevance of replicating and extending the present outcomes, investigating further parameters of stimulation and its effects on other indirect markers of LC-NE activity.