In the world, the COVID-19 pandemic has led to public mental health stress, anxiety, panic, and behavioral disorders. The purpose of the present study was to examine whether meaning in life mediated the relationship between coronavirus stress and depressive symptoms and whether the mediating effect of meaning in life on depressive symptoms was moderated by optimism. The sample of the study included 475 undergraduate students attending a public university in an urban city of Turkey. They were 69.2% female, ranged in age between 18 and 34 years (M = 20.63, SD = 1.99). Results showed that meaning in life and optimism–pessimism mediated the relationship between coronavirus stress and depressive symptoms. Optimism also mediated the relationship between meaning in life and depressive symptoms. Furthermore, optimism moderated the mediating effect of meaning in life in the relationship between coronavirus stress and depressive symptoms. These results indicated that the relationship between coronavirus stress and depressive symptoms can be better understood by meaning in life and optimism. Optimism may play a protective factor to mitigate the impact of stress on depressive symptoms