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Sleepiness during work hours is the most common complaint of night shift workers, and is a sensitive indicator of performance decrements. Sleepiness levels vary between individuals, yet few have investigated individual factors as predictors of night shift sleepiness, and these have shown mixed results. We aimed to examine the effects of bio-psycho-social factors on subjective sleepiness of nurses during the night shift.Female nurses (n=119) working irregular rotating shifts were recruited from two hospitals in Northern Israel, using convenience sampling by clusters. Inclusion criteria were working at least 75% of full time, with at least one night shift per week. Exclusion criteria were pregnancy, a diagnosed sleep disorder, and/or chronic medical conditions. Subjective sleepiness was measured hourly during two night shifts using the Karolinska Sleepiness Scale (KSS). Sleep was monitored by actigraphy 24 hours before and until the end of the night shifts. Participants completed a socio-demographic questionnaire, the Munich ChronoType Questionnaire for Shiftwork (MCTQshift), the Pittsburg Sleep Quality Index (PSQI) and the Pre-Sleep Arousal Scale (PSAS).Mixed models stepwise analyses found main effects for hour, age, cognitive pre-sleep arousal and number of children on nighttime sleepiness (all p<0.01). Effects of chronotype on sleepiness were inconsistent. Interactions were found for age*number of children (p<0.01), pre-sleep cognitive arousal*chronotype (p<0.05), and age*chronotype (p=0.06). Older nurses were less sleepy than younger nurses, but this impact was attenuated by early chronotype and having more children. High cognitive pre-sleep arousal, but not sleep, predicted increased sleepiness, especially in nurses with late chronotype.The impact of bio-psycho-social factors on night shift sleepiness is complex and depends on mutual interactions between these factors. Nurses who are young, late chronotypes and with high cognitive pre-sleep arousal require special attention and support, and must develop personal strategies for maintaining vigilance on the night shift.