Objective: Examine predictors of alcohol misuse among university students amid the COVID-19 pandemic. Participants: University students who completed the National College Health Assessment III before, during, and after the pandemic lockdown. Methods: Using multivariable logistic regression, we examined associations between psychological functioning, time spent with family and friends, and problematic alcohol use. Results: Alcohol use decreased, and psychological functioning was poorest one year after COVID-19-related university closures. While indicators of psychological functioning started to improve in the second year after the school closures, alcohol use started to increase. Overall stress, spending more time with friends, and fraternity/sorority residence significantly predicted moderate to high risk for alcohol dependence and binge drinking two years post-pandemic. Severe psychological distress (OR= 1.36, CI = 1.22, 1.52, p < 0.001) predicted moderate to high risk for alcohol dependence but not binge drinking. Conclusion: Innovative mental health interventions are needed to reduce alcohol misuse among university students.