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Abstract Background Health care workers caring for patients with COVID-19 pandemic are prone to extraordinary stressors and psychological problems. The aim of this study was to estimate the prevalence and risk factors of major depressive disorder among health care providers who are caring for patients with COVID-19. Methods Two hundred-seventy of health care workers were screened for depressive symptoms by DASS-21 Questionnaire. Only 152 of the participants accepted to be interviewed using SCID-I for diagnosis of major depressive disorder. Results According to DASS-21, 28.1% of HCWs had mild-to-moderate depressive symptoms, and 64.8% with severe symptoms. Of 152 who were interviewed using SCID-I, 74.3% were diagnosed with major depression disorder. Young age, decreased sleep hours, female sex, past history of a psychiatric disease, fear of COVID-19 infection for themselves or their relatives, and fear of death with COVID-19 for themselves or their relatives were significant predictors for major depressive disorder and its severity. Conclusion Major depressive disorder is common among HCWs during COVID-19 pandemic. Screening for depression, particularly for young females, and early treatment are recommended.