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Background  Many university students experience high levels of study-related fatigue. This high prevalence, and the negative impact of fatigue on health and academic performance, call for prevention and reduction of these symptoms. The primary aim of the current study was to investigate to what extent an exercise intervention is effective in reducing three indicators of study-related fatigue (emotional exhaustion, overall fatigue, and need for recovery). Effects of exercise on secondary outcomes (sleep quality, self-efficacy, physical fitness, and cognitive functioning) were also investigated.    Methods  Participants were students with high levels of study-related fatigue, currently not exercising or receiving other psychological or pharmacological treatments, and with no medical cause of fatigue. They were randomly assigned to either a six-week exercise intervention (low-intensity running three times a week,  n  = 49) or wait list (no intervention,  n  = 48). All participants were measured before the intervention (T0), and immediately after the intervention (T1). Exercisers were also investigated 4 weeks (T2) and 12 weeks (T3) after the intervention.    Results  Participants in the exercise condition showed a larger decrease in two of the three indicators of study-related fatigue (i.e., overall fatigue and need for recovery) as compared to controls. Additionally, sleep quality and some indicators of cognitive functioning improved more among exercisers than among controls. No effects were found for self-efficacy, and physical fitness. The initial effects of the exercise intervention lasted at follow-up (T2 and T3). At 12-week follow up (T3), 80% of participants in the exercise condition still engaged in regular exercise, and further enhancements were seen for emotional exhaustion, overall fatigue, and sleep quality.    Conclusions  These results underline the value of low-intensity exercise for university students with high levels of study-related fatigue. The follow-up effects that were found in this study imply that the intervention has the potential to promote regular exercise and accompanying beneficial effects in the longer run.    Trial Registration  Netherlands Trial Register  NTR4412

Exercise as an Intervention to Reduce Study-Related Fatigue among University Students: A Two-Arm Parallel Randomized Controlled Trial