The reasons underlying some individuals’ negative reactions to profound societal and organizational changes are still unclear. We argue that collective relative deprivation (i.e., feelings of discontent arising from group-based threat) mediates the relationship between perceptions of change and employees’ psychological reactions. Specifically, we tested the hypothesis that when employees perceive organizational change to be negative and rapid, they are more likely to sense collective relative deprivation. This sense of collective relative deprivation, in turn, leads to higher levels of psychological distress and burnout symptoms. We tested the mediator role of collective relative deprivation among a group of nurses, and confirmed these hypotheses through a path analysis and a bootstrap procedure. The discussion underlines both theoretical and applied contributions, particularly in the modern context of vast and profound organizational changes.