Purpose: The purpose of this study was to identify associations among the sleep disturbance, fatigue, job stress, and blood and body fluid (BBF) exposure of shift-work nurses. Methods: A total of 299 shift-work nurses from two tertiary hospitals were enrolled in this study. We used the Insomnia Severity Index (ISI), and the Fatigue Severity Scale (FSS), and the Korean Occupational Stress Scale-Short Form (KOSS-SF) to evaluate sleep disturbance, fatigue, and job stress, respectively. The data were analyzed using t-test or chi-squared test and Logistic regression analysis using the SPSS 23.0 program. Results: We found that 43.8% of participants reported BBF exposure over the past year. Splash or exposure to broken skin of BBF were most frequent (56.9%), and followed by needlestick injuries (30.4%) and sharp injuries (12.8%). Age, hospital, working period, level of stress, sleep disturbance (ISI≥15), fatigue (FSS score≥4), job demand and organizational climate subset in KOSS-SF were significantly associated with BBF exposure in shift-work nurses. In multivariate analysis after adjusting age and hospital, the risk factors of BBF exposure in shift-work nurses were the level of stress and fatigue (FSS score≥4). Conclusion: Fatigue and job stress were related to BBF exposure in shift-work nurses. Our results suggest that management of sleep disturbance, fatigue, and high job stress in shift-work nurses is needed to reduce risk of BBF exposure.