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Background There is an increasing evidence of an association between low vitamin-D levels and depression. Consequently, the present study aimed to investigate the serum levels of vitamin D in cases with major depressive disorder in Sohag Governorate in Upper Egypt. Also, we studied the correlation between serum vitamin-D level and different demographic and clinical variables in these patients. This study included 60 patients who attended our outpatient psychiatric clinic at Sohag University Hospital, who were diagnosed as major depressive disorder (group I) and a similar number (60) of age-matched and sex-matched controls (group II). The diagnosis was based on Diagnostic and statistical manual of mental disorders, 5th ed. criteria and verified by application of Quick Inventory of Depressive Symptomatology. A blood sample was taken from all participants for assessment of the levels of serum vitamin D. Results Patients with major depressive disorder have significantly lower serum vitamin-D levels than controls (mean±SD was 17.2±12.3 for patients and 33.4±24.2 for controls, P=0.001). About 58.33% of patients had deficient vitamin D, while 45% of controls had deficient vitamin D (P=0.022). There is a statistically significant negative correlation between the severity of depression and serum vitamin D. Conclusions Serum vitamin D was significantly lower in major depression patients than controls. In addition, it is evident to have a direct correlation with severity of symptom depression. [ABSTRACT FROM AUTHOR]