Aircrew fatigue constitutes a safety hazard in aviation, which authorities attempt to mitigate through flight time limitations. Some gaps in knowledge exist, however. The purpose of the present study was to investigate the associations of schedule characteristics with fatigue and amount of sleep in the acute 24-h window, and as cumulative effects across the 7-day work period. One hundred and six aircrew (14% cabin crew) participated. They rated fatigue on the Karolinska Sleepiness Scale (KSS) three times per flight day for four 7-day work periods, with up to 7 days off between work periods. Mixed model regression was applied to the data. In the multivariable model, more sleep was associated with lower fatigue (p = .000)), corresponding to 0.26 KSS units less per hour of sleep. Very early, early and late duty types, as well as duty time, were associated with higher fatigue. For the 7-day work period, accumulation of very early duties and longer duty time were associated with increased fatigue, and more accumulated sleep was associated with lower fatigue in the adjusted model (0.08 KSS units per hour of sleep) (p = .000). Accumulated duty time was not significant when analysed as a single variable, but became so after adjustment for sleep. The results suggest that sleep, duty time and early starts are important predictors of fatigue in the 24-h window and that the number of very early starts and short sleep have cumulative effects on fatigue across a 7-day work period.