Abstract Background During the COVID-19 epidemic in China, clinical nurses are at an elevated risk of suffering fatigue. This research sought to investigate the correlation between dispositional mindfulness and fatigue among nurses, as well as the potential mediation role of sleep quality in this relationship. Methods This online cross-sectional survey was performed from August to September 2022 to collect data from 2143 Chinese nurses after the re-emergence of COVID-19. The significance of the mediation effect was determined through a bootstrap approach with SPSS PROCESS macro. Results Higher levels of dispositional mindfulness were significantly negatively related to fatigue (r = -0.518, P