Objectives: Although loneliness and stress have been widely implicated in worse mental health outcomes for college students, the relationship between them remains poorly understood. Participants: Data were collected from 111 undergraduates at a large Midwestern university in fall 2019 - winter 2020. A subset (N = 34) of those responded to a follow-up survey during the COVID-19 pandemic (May 2020). Methods: At both time points, participants completed measures of loneliness and stress, as well as well-validated measures of depression and anxiety. Results: Prior to the pandemic, stress mediated the positive relationship between loneliness and depression. During the pandemic, mental health outcomes, stress, and loneliness all increased. Stress, but not loneliness, predicted college students' worse mental health outcomes during the pandemic. Conclusions: Stress plays a key role in college students' worsening mental health. Reducing loneliness may be a potential strategy to mitigate the negative impact of stress on college students' mental health.