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The purpose of this study was to examine the relationships between college students’ individual, interpersonal, institutional, health and safety, and academic/financial stressors and odds of clinically significant major depressive disorder (MDD) and generalized anxiety disorder (GAD) during the COVID-19 pandemic. We drew our sample from eight large, public research universities (n = 27,131). The results of logistic regressions suggest there are several demographic variables associated with students’ odds of MDD or GAD. Additionally, supportive campus environments are associated with reduced odds of MDD or GAD while food/housing insecurity, lack of safety in home environment, academic obstacles to online instruction, and financial hardships increased odds of MDD or GAD.