Objective: To assess the influence of specific COVID-19 impacts on college student depression, loneliness, and alcohol and cannabis use, and to investigate if resilience moderates these relationships. Participants: Data were collected from students (N = 1849, 80.9% white, 66.6% female) at a midwestern university during the 2021 winter/spring semester. Methods: Data were gathered cross-sectionally through an online survey platform. COVID-19 impacts and resilience's relationships with mental health variables were analyzed with multiple regression analysis. Moderation analyses were conducted using PROCESS. Results: The COVID-19 impacts measured in this study were significantly related to student depression and cannabis use. Resilience moderated the association between COVID-19 impacts and (a) depression and (b) cannabis use. Conclusion: Resilience may mitigate the effect of pandemic-related impacts on depression and cannabis use in college students, but not loneliness and alcohol use. These findings hold important implications for further research and practice.