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The COVID-19 disruption presented considerable challenges for university students, requiring the sudden need for increased engagement in remote learning environments and the ability to cope with academic and familial demands. To examine how students self-regulated their learning during the disruption, we surveyed undergraduates (n = 226) enrolled in four sections of a large biology course once during the first week of the semester, immediately after the disruption, and through the end of the semester. The results indicated significant decreases in student motivation, increases in students' perceived costs, and quadratic changes in self-reported coping strategies and mental depletion during disrupted learning. In a final model, students' self-efficacy and perceptions of cost, as well as feelings of anger and personal responsibility for family combined to form a parsimonious set of predictors that explained variance in course performance.