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The COVID-19 pandemic caused severe disruptions in living and learning to millions of college students. We investigated two dimensions of anxiety that were specific to the pandemic – COVID-19 related anxiety and COVID-19 vaccine anxiety – to evaluate their relationship to college adjustment during the pandemic using mediation analysis. Using cross-sectional survey data across three semester waves (Spring 2021, Fall 2021, and Spring 2022), we probed whether anxiety acted as a challenge or hindrance stressor on adjustment. We found that although anxiety decreased in both COVID-19 dimensions across semesters, student adjustment to college remained consistently low. Our mediation analysis revealed that both COVID-19 anxiety and COVID-19 vaccine anxiety acted as challenge stressors, elevating academic, social, personal-emotional, and institutional adjustment during the pandemic.