Background and Purpose: This study aims to reveal the relationships between change fatigue and perceived organizational culture, burnout, organizational commitment, and turnover intention; to examine the effects of change fatigue on burnout, turnover intention, and organizational commitment; to determine whether there is any mediator effect of burnout on the relation between change fatigue, organizational commitment, and turnover intention or not; and finally, to determine the effects of organization culture on change fatigue. Methods: This cross-sectional study was conducted on 403 nurses working in a university hospital in Erzincan, Türkiye. Multiple and hierarchical regression analyses were used to determine the relationships between change fatigue, organizational culture, burnout, turnover intention, and organizational commitment. Results: As a result of the analysis, it was determined that change fatigue has a significantly positive effect on burnout and turnover intention and a negative effect on organizational commitment. In addition, it was revealed that burnout has a partial mediating effect on the relationship between change fatigue, turnover intention, and organizational commitment. Moreover, it was found that clan and adhocracy cultures, which are perceived organizational culture types, have a negative effect on change fatigue, and a hierarchical culture has a significantly positive effect. Implications for Practice: To prevent change fatigue, managers of health institutions can be advised to inform nurses about the process before each change initiative. In addition, creating a culture in the organization that adopts respect and understanding as a philosophy, is based on employee participation, and exhibits modern leadership behaviors.