BackgroundShift work is inevitable for nurses in intensive care units. Various studies explored nurses' fatigue in multiple hospital wards. However, few studies focused on fatigue among nurses in intensive care units.AimsTo determine the association between shift work schedules, compensatory sleep, work–family conflict, and fatigue of shift‐working nurses in critical care units.DesignA descriptive cross‐sectional multi‐center study was conducted in March 2022 among intensive care nurses from five hospitals.MethodsData were collected by online survey, including self‐designed demographic questions, the Fatigue Scale‐14, the Chinese adult daytime sleepiness scale, and the work‐family scale. Pearson correlation was conducted for bivariate analysis. Independent‐sample t‐test, one‐way ANOVA, and multiple linear regression analysis were performed to examine fatigue‐related variables.ResultsA total of 326 nurses responded to the survey with an effective response rate of 74.9%. The mean scores of physical fatigue and mental fatigue were 6.80 and 3.72, respectively. The bivariate analyses showed that work–family conflict was positively correlated with physical (r = 0.483, p < .001) and mental fatigue (r = 0.406, p < .001). Multiple linear regression results showed that work–family conflict, daytime sleepiness, and shift system were statistically significant factors influencing physical fatigue (F = 41.793, p < .001). Work–family conflict, sleep duration after the night shift, and daytime sleepiness were the main influencing factors of mental fatigue (F = 25.105, p < .001).ConclusionsNurses with higher work–family conflict, daytime sleepiness, and working 12‐h shifts have higher levels of physical fatigue. Higher work–family conflict, shorter sleep duration after night shifts, and daytime sleepiness are associated with higher mental fatigue among intensive care nurses.Relevance to Clinical PracticeNursing managers and nurses should consider work‐family factors and compensatory sleep in their efforts to reduce fatigue. It is necessary to strengthen work‐supporting strategies and compensatory sleep guidance for nurses to promote fatigue recovery.