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Employees frequently have to use various media to complete multiple tasks at work, and depression has become a common problem influencing their mental health and work efficiency. We conducted a survey to investigate the relationship between the media multitasking and depression of 490 employees of a state-owned enterprise in China. The results showed that media multitasking was positively correlated with employee depression. Moreover, ego depletion significantly mediated the relationship between media multitasking and depression, and self-control moderated the relationship between ego depletion and depression. Greater self-control may help buffer the effect of ego depletion on depression. These results have theoretical and practical implications for improving employees’ mental health during China’s enterprise transformation process.