PURPOSE: Isolation policies are long-term and strictly enforced in China during the COVID-19 outbreak. Social media might be widely used for communication, work, understanding the development of the epidemic, etc. However, these behaviors might lead to problematic social media use. The present study investigated the effect of stressors of COVID-19 on problematic social media use, as well as the internal mechanisms involved. METHODS: One thousand three hundred seventy-three Chinese college students ( = 19.53, = 1.09) were recruited randomly from four grades who completed Coronavirus Stress Scale, Fear of Missing Out Scale, Problematic Mobile Social Media Usage Assessment Questionnaire, and Regulatory Emotional Self-Efficacy Scale. RESULTS: Stressors of COVID-19 were positively related to problematic social media use. The link between stressors of COVID-19 and problematic social media use was mediated by fear of missing out. Additionally, the association between fear of missing out and problematic social media use, as well as the association between stressors of COVID-19 and problematic social media use were moderated by regulatory emotional self-efficacy. CONCLUSION: The current findings reveal the mechanism that may be used to reduce the likelihood of problematic social media use in the context of the COVID-19 outbreak. To prevent and intervene in problematic social media use during the COVID-19 pandemic, this study stressed the importance of decreasing the fear of missing out and enhancing regulatory emotional self-efficacy.