Objective: Given the importance of COVID-19 consequences and students’,health, this study aimed to predict the fear of COVID-19 based on spiritual well-being and self-efficacy among Iranian university students by focusing on the mediating role of mindfulness. Methods: This study was a descriptive correlational study. An online sampling method was used, and the sample included 396 university students in Tehran City, Iran. Mindful Attention Awareness Scale (MAAS), general self-efficacy scale, fear of COVID-19 scale, and Paloutzian and Ellison’, s spiritual well-being scale were used for data collection. An independent t test, the Pearson correlation, and the regression test were used to analyze the obtained data. Results: The results show that the overall effects of religious well-being (β, =-0. 192, P=0. 001), existential well-being (β, =-0. 227, P=0. 001), and self-efficacy (β, =-0. 093, P=0. 013) were significant. The indirect effects of religious well-being (β, =-0. 026, P=0. 001), existential wellbeing (β, =-0. 013, P=0. 016), and self-efficacy (β, =-0. 04, P=0. 001) were significant, too. The direct effects of religious well-being (β, =-0. 253, P=0. 001), existential well-being (β, =-0. 205, P=0. 016), and self-efficacy (β, =-0. 133, P=0. 013) were significant, as well. Conclusion: Spiritual well-being, self-efficacy, and mindfulness are associated with a reduction in perceived fear of COVID 19 in Iranian students, and mindfulness has a role in these relationships.