Objective:To explore the current status of mental workload and its relationship with work engagement and fatigue, as well as the impact path among the three.Methods:Clinical nurses from six tertiary hospitals including Shanghai Traditional Chinese Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, etc. were selected to conduct a cross-sectional survey using convenience sampling method from February to March 2020. They were investigated by general information questionnaire, NASA Task Load Index (NASA-TLX), Utrecht Work Engagement Scale (UWES), and Fatigue Scale-14 (FS-14).Results:The total mental workload score of 776 clinical nurses was 76.50(69.00, 84.00). Single factor analysis showed that clinical nurses of different ages, marriage and childbirth status, education level, professional title and working years had different mental workload ( Z = -2.61, H values were 10.22-22.41, all P<0.01). Bivariate analysis revealed that the mental workload of clinical nurses was positively correlated with work engagement ( r = 0.27, P<0.01) and fatigue ( r = 0.23, P<0.01), and work engagement and fatigue were negatively correlated ( r = -0.23, P<0.01). Mediation effect analysis demonstrated that mental workload had a positive predictive effect on fatigue ( β = 0.39, P<0.01) and work engagement ( β = 0.35, P<0.01); the suppressing effect of work engagement between mental workload and fatigue, the absolute value of the ratio of the suppressing effect to the direct effect was |-0.17/0.39|. Conclusions:The mental workload of clinical nurses is at relatively high level. Hospital administrators can partially improve the fatigue state of clinical nurses with high mental load through the adjustment effect of work engagement.