Objective: Associations between mindfulness and improved physical and psychological health have been established, but COVID-19 presents a novel context. This study examined the relationship between individual mindfulness facets and general stress among college students experiencing at least one symptom of acute COVID-19 infection in the context of the pandemic. Methods: Five hundred sixteen university students experiencing at least one CDC-identified COVID-19 symptom completed measures of general stress, mindfulness, and somatic symptoms in 2020-2021 during the COVID-19 pandemic following IRB approval and informed consent. Results: The act with awareness, nonjudgment, and nonreactivity facets of mindfulness were associated with general stress. In total, the model accounted for over half of the variance in general stress (R2 = 0.51, p < 0.001). Conclusion: Mindfulness may be particularly important in explaining general stress among college students reporting a symptom of COVID-19. Mindfulness may benefit college students as the pandemic continues to unfold, and monitoring one’s physical health remains a primary mitigation strategy. These results may also inform understanding and responses to future public health emergencies in which monitoring somatic symptoms is encouraged by public health officials to contain the spread.