Aims: The impact of the extent of mentally demanding work on the next-day’s strain is largely unknown, as existing studies generally investigate consequences of extended versus normal workdays. The present study sought to fill this gap by investigating how short work periods of mentally demanding academic work impact strain reactions in medical students preparing for an exam, using days of no work as reference category. Method: The observational design involved students repeatedly self-reporting fatigue, vigor, distress, and the preceding day’s study duration. Hours of nocturnal sleep, attending paid work and compulsory classes, gender, and proximity to the exam were controls in the linear model (generalized estimating equations). Forty-nine students provided 411 self-reports (M = 8.6, SD = 7.0 self-reports/student). Results: Engaging in mentally demanding work was associated with increased distress and work periods > 4 h with increased fatigue. Distress, vigor loss, and fatigue increased in proximity to the exam. Conclusion: Despite students’ high control of their schedule, even short periods of mentally highly demanding work may impair next-day’s well-being when task motivation is high. Freelancers and students might require health-promoting scheduling of work and leisure to avoid an accumulation of strain.