OBJECTIVE: Mindfulness is a promising psychological resource that can alleviate dysfunctional fear responses and promote mental health. We investigated how mindfulness affects fear and depression in isolated patients with coronavirus disease 2019 (COVID-19), and whether it acts as a mediator. METHODS: We conducted an online survey of COVID-19 patients undergoing at-home treatment from February to April 2022. The survey included a questionnaire on fear of COVID-19 (measured by the Fear of COVID-19 Scale), mindfulness (measured by the Mindful Attention Awareness Scale), and depression (measured by the Patient Health Questionnaire). A total of 380 participants completed the questionnaire. We analyzed the correlation between each variable and performed a mediation analysis using hierarchical regression and bootstrapping to verify the statistical significance of the mediating effects. RESULTS: Each variable was significantly correlated. Hierarchical regression analysis showed that the association between the fear of COVID-19 and depression decreased from 0.377-0.255, suggesting that mindfulness partially mediates the relationship between fear of COVID-19 and depression. Bootstrapping analysis showed that the indirect effect of the mediating variable (mindfulness) is 0.121, which accounts for 32.3% of the total effect. CONCLUSIONS: Interventions that promote mindfulness in patients with acute COVID-19 may be beneficial for their mental health.