Purpose: This study aimed to identify the predictors of blood and body fluid exposure (BBFE) in multifaceted individual (sleep disturbance and fatigue), occupational (occupational stress), and organizational (hospital safety climate) factors, as well as infection prevention behavior. We also aimed to test the mediating effect of infection prevention behavior in relation to multifaceted factors and the frequency of BBFE. Methods: This study was based on a secondary data analysis, using data of 246 nurses from the Shift Work Nurses’ Health and Turnover study. Based on the characteristics of zero-inflated and over-dispersed count data of frequencies of BBFE, the data were analyzed to calculate zero-inflated negative binomial regression within a generalized linear model and to test the mediating effect using SPSS 25.0, Stata 14.1, and PROCESS macro. Results: We found that the frequency of BBFE increased in subjects with disturbed sleep (IRR = 1.87, p =.049), and the probability of non-BBFE increased in subjects showing higher infection prevention behavior (IRR = 15.05, p = .006) and a hospital safety climate (IRR = 28.46, p = .018). We also found that infection prevention behavior had mediating effects on the occupational stress-BBFE and hospital safety climate-BBFE relationships. Conclusion: Sleep disturbance is an important risk factor related to frequency of BBFE, whereas preventive factors are infection prevention behavior and hospital safety climate. We suggest individual and systemic efforts to improve sleep, occupational stress, and hospital safety climate to prevent BBFE occurrence.