•The paper presents a study investigating the intricate relationship between work demands, off-work demands, persistent fatigue, sleep patterns, and daily unsafe driving behaviors among hospital nurses.•By using an intensive diary study employing a multilevel longitudinal approach, the study identifies sleep duration as a key factor that mitigates the indirect relationships between demands, persistent fatigue, and unsafe driving. The study, however, did not find statistically significant evidence regarding the conditional indirect effect of sleep quality on unsafe driving via persistent fatigue.•These findings highlight the critical role of sleep duration as a potential mitigating factor against fatigue-induced unsafe driving among nurses, emphasizing the importance of sleep in promoting commuter safety. Hospital nurses frequently experience persistent fatigue and suboptimal sleep, potentially leading to unsafe driving behaviours. The increasing demands placed on nursing services may exacerbate this issue, given the global shortage of nurses, yet this complex relationship and how it affects nurses on a day-to-day basis remains largely underexplored. This study investigates the relationships between work demands, off-work demands, persistent fatigue, and daily unsafe driving among nurses while commuting. Using a multilevel diary study spanning five to seven consecutive days, 172 hospital nurses provided 976 data points with three momentary points per day (T1-T3). Hierarchical Linear Modeling (HLM) and Monte-Carlo methods for assessing mediation (2–1-1) and moderated mediation were applied to explore the complex interactions between work demands, off-work demands, persistent fatigue, sleep duration, sleep quality, and unsafe driving. The model was controlled for various factors such as age, gender, number of children, commuting impedance, within-person work demands, and off-work demands. Results revealed positive associations between between-person work demands, off-work demands, persistent fatigue, and unsafe driving while commuting to work on the next shift. Sleep duration was identified as a key factor mitigating the indirect relationships between individual demands, persistent fatigue, and unsafe driving. However, the study did not find significant evidence regarding sleep quality's influence on unsafe driving through persistent fatigue. Overall, this research sheds light on the intricate relationships among work demands, persistent fatigue, sleep, and daily unsafe driving, emphasizing the critical role of sleep in attenuating fatigue-induced risks during nurses' commutes.