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In February 2020, the Novel Coronavirus (COVID-19) was raging in Wuhan, China and quickly spreading to the rest of the world. This period was fraught with uncertainty for those in the affected areas. The present investigation examined the role of two potential coping resources during this stressful period of uncertainty: flow and mindfulness. Participants in Wuhan and other major cities affected by COVID-19 (N = 5115) completed an online survey assessing subjective experiences of flow, mindfulness, and well-being. Longer quarantine was associated with poorer well-being; flow and mindfulness were associated with better well-being on some measures. However, flow—but not mindfulness—moderated the link between quarantine length and well-being, such that people who experienced high levels flow showed little or no association between quarantine length and poorer well-being. These findings suggest that experiencing flow (typically by engaging in flow-inducing activities) may be a particularly effective way to protect against potentially deleterious effects of a period of quarantine.