Fatigue, a prevalent symptom in today’s general population, has been found to play a critical role in individuals’ well-being, health, and occupational outcomes. The relationship between information technology (IT) and fatigue has long been investigated in psychological literature, whereas the IS field has paid insufficient attention to this topic. The present research aims to conceptualize IT fatigue and examine its impact on users’ task performance. Drawing upon the theory of fatigue from the cognitive psychology discipline, we propose four dimensions of IT fatigue: general IT fatigue, reduced motivation to use IT, reduced concentration on IT, and physical IT fatigue. Further, we argue that IT mindfulness can potentially reduce users’ IT fatigue and at the same time moderate the relationship between IT fatigue and task performance. It is expected that the investigation into the IT-induced fatigue phenomenon will assist future research on fatigue in the context of human-technology interaction.