Background: Major depressive disorder (MDD) is a major health concern, with lifetime prevalence. In the United States estimated to be as high as 16.2%. Although, a number of pharmacological agents are available to treat, approximately 30–40% of patients do not respond to treatment. Therefore, a major emphasis in modern psychiatric research is to uncover the underlying etiology of mood disorders, and to develop novel efficacious antidepressant treatments. Oxytocin may be of therapeutic benefit in these patients. Objective: To assess the level of oxytocin in patients with major depressive disorders. Patients and methods: A case-control study was conducted on sixty subjects above eighteen years old. They were classified into: 20 naïve patients during the manic attack of bipolar manic depressive disorder (group I), 20 naïve patients during the depressive attack of bipolar manic depressive disorder (group II) and 20 normal control subjects (group ІІІ). All participants were subjected to full history, clinical examination and laboratory measurement of oxytocin, AST, ALT, serum albumin, BUN & creatinine. Results: On comparing group I (bipolar patients with recent attack of mania) and group 3 (control) regarding serum oxytocin level, there was a significant difference in serum oxytocin being higher in patients with manic symptoms (p < 0.001) but with no significant difference between group 2 (bipolar patients with recent attack of depression) and group 3 (control). Conclusion: The significant difference in the level of oxytocin among the studied groups may suggest a possible role of oxytocin in management of patients with such psychiatric disorder.