Purpose: This study examines why and when nurses' role ambiguity leads to their work alienation during the COVID-19 pandemic. Design/methodology/approach: Survey data were collected from 335 hospital nurses in Ma’anshan, China. The data were analyzed using hierarchical regression and bootstrapping. Findings: Occupational disidentification mediated the relationship between role ambiguity and work alienation. This mediating effect was not significant when nurses possessed a high level of perceived climate of prioritizing COVID-19 infection prevention (PCIP). Practical implications: To reduce nurses' work alienation in a pandemic situation, the hospital management team should pay attention to and try to minimize the nurses' role ambiguity and occupational disidentification. When doing so, the management team will find it particularly helpful if they can make nurses perceive a strong climate of PCIP. Originality/value: This study contributes to the existing knowledge of role ambiguity and work alienation by highlighting occupational disidentification as a mediator after controlling for organizational identification in the context of COVID-19. It further demonstrates when the mediating role of occupational disidentification is likely to be strong or weak by studying the moderating effect of perceived climate of PCIP.