BACKGROUND: Higher education students exhibit heightened sensitivity to environmental changes as they navigate the critical transition from adolescence to adulthood. The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to universities worldwide, exemplifying a crisis that profoundly affects the learning outcomes and psychological status of college students. Although it is known that campus lockdown has triggered dramatic changes in lifestyles, learning outcomes, and psychological statuses, in-depth knowledge of the causal relationships among these changes remains largely unclear. METHODS: Here, we conducted a cross-sectional survey designed to assess the impact of campus closure during COVID-19 on lifestyle, educational performance, and anxiety levels among college students. We surveyed over 3,500 junior college, undergraduate and graduate participants from 94 colleges/universities across 30 provinces, municipalities, and autonomous regions in China.We employed structural equation modeling (SEM) to explore the relationships between changes in lifestyle, educational performance, and levels of anxiety associated with campus open or closure regulations during the COVID-19 pandemic. RESULTS: Our results discovered that sleep duration, physical activity involvement, and social connections were crucial for sustaining students' learning outcomes and mental health. The shift to online learning and campus lockdown exacerbated stressors, contributing to heightened anxiety (β = 0.066), disrupted sleep patterns, and enhanced physical activity (β = 0.070) and reduced learning effect (β = -0.059). Sleep patterns were disrupted by the campus lockdown, an effect mediated by the degradation of relationships among classmates. Nonetheless, the best-fitting SEM uncovered the intricate relationships among lifestyle changes, learning outcomes, and psychological status in response to sudden environmental changes (Fisher's C = 80.949, P = 0.328). These results highlight the critical role of adaptable, supportive campus policies tailored to meet the diverse needs and interests of students during and beyond crises (Fisher's C = 59.568, P = 0.809). CONCLUSIONS: Our study advocates for a holistic approach that addresses the multifaceted aspects of student life to cultivate a resilient academic community. This approach contributes to a deeper understanding of the effects of sudden environmental changes on students' psychological well-being and academic performance in the post-pandemic era.