The objective of this study was to compare the development of sleepiness during manual driving versus level 2 partially automated driving, when driving on a motorway in Sweden. The hypothesis was that partially automated driving will lead to higher levels of fatigue due to underload. Eighty-nine drivers were included in the study using a 2 × 2 design with the conditions manual versus partially automated driving and daytime (full sleep) versus night-time (sleep deprived). The results showed that night-time driving led to markedly increased levels of sleepiness in terms of subjective sleepiness ratings, blink durations, PERCLOS, pupil diameter and heart rate. Partially automated driving led to slightly higher subjective sleepiness ratings, longer blink durations, decreased pupil diameter, slower heart rate, and higher EEG alpha and theta activity. However, elevated levels of sleepiness mainly arose from the night-time drives when the sleep pressure was high. During daytime, when the drivers were alert, partially automated driving had little or no detrimental effects on driver fatigue. Whether the negative effects of increased sleepiness during partially automated driving can be compensated by the positive effects of lateral and longitudinal driving support needs to be investigated in further studies. © 2021 The Author(s)