Objective: The neuropeptide arginine vasopressin (AVP) has effects on behavior and stress regulations which are impaired in bipolar disorder (BD). Only a very limited number of studies have investigated AVP levels in bipolar disorder in contrast to depressive disorders. The study aimed to investigate serum AVP levels during the manic, depressive, or remission periods and after treatment response in patients with bipolar I disorder (BD-I) and healthy controls. Methods: The study consisted of 67 patients with BD-I and 24 healthy controls. The patients were in the manic, depressive, or remission periods of BD-I. Serum AVP levels were assayed in the three groups of patients with BD-I and the controls at the study onset. Then, a second measurement of the AVP levels were carried out in the manic or depressive periods after treatment response. The treatment response was defined as a 50% decrease in the young mania rating scale and the Hamilton Depression Rating Scale scores for manic and depressive episodes, respectively. Results: The main finding was the significantly lower serum AVP levels in BD-I during manic, depressive, or remission periods compared to healthy controls. After-treatment-response serum AVP levels in depressive BD-I patients increased to the levels of healthy controls and became higher than in the remission period of BD-I. Conclusions: The global reduction in serum AVP levels may be an indicator of impaired neuronal function and neuroprogressive deterioration seen in BD. Notably, given the increased AVP levels in major depressive disorder, serum AVP levels may contribute to distinguishing depressive BD-I from major depressive disorder.