Objective To investigate the level of change fatigue among clinical nurses, to analyze its latent profile characteristics and influencing factors, so as to provide references for developing targeted management strategies. Methods Using a convenience sampling method, a total of 632 clinical nurses from three grade A tertiary general hospitals were selected and investigated by utilizing a general information questionnaire, the Change Fatigue Measurement Scale, and the Perceived Organizational Support Scale from January to March 2025. Latent profile analysis was conducted to assess nurses′ change fatigue, and univariate analysis along with multivariate logistic regression analysis were used to identify the influencing factors of different categories. Results The participants′ change fatigue score was (26.97±7.23) points. Clinical nurses′ change fatigue could be categorized into three latent classes:low fatigue-change adaptive type (18.51%), moderate fatigue-passive endurance type (55.06%), and high fatigue-burnout type (26.43%). Logistic regression analysis indicated that, age, average monthly income, and perceived organizational support were the influencing factors of different latent profiles (all P<0.05). Conclusion Nurses′ change fatigue is at a moderate level with distinct categorical characteristics. Nursing administrators should implement targeted interventions based on the identified influencing factors associated with different latent profiles to effectively reduce change fatigue levels among clinical nurses.