Abstract Background Depression disorders are a leading cause of disability in the world which imposes a significant economic burden on patients and societies The present study aimed to determine the economic burden of Major Depressive Disorder (MDD) on the patients referred to the reference psychiatric single-specialty hospitals in southern Iran in 2020. Methods This cross-sectional research is a partial economic evaluation and a cost-of-illness study conducted in southern Iran in 2020. A total of 563 patients were enrolled through the census method, and a researcher-made data collection form was used to gather the required information. The prevalence-based and the bottom-up approaches were also used to collect the cost information and calculate the costs, respectively. The data on direct medical, direct non-medical, and indirect costs were obtained using the information in the patients’ medical records and insurance bills as well as their self-reports or those of their companions. To calculate the indirect costs, the human capital approach was used as well. Results The results showed that the annual cost of MDD was $ 2717.41 Purchasing Power Parity (PPP) (USD 2026.13) per patient in 2020. Direct medical costs accounted for the largest share of the costs (73.68%), of which hoteling and regular beds expenses were the highest (57.70% of the total direct medical costs). The shares of direct non-medical and indirect costs were 7.52 and 18.80%, respectively, and the economic burden of the disease in the country was estimated at $7,120,456,596 PPP (USD 5,309,088,699). Conclusion In general, due to the high prevalence of MDD and the chronicity of the disease, the costs of its treatment can impose a heavy economic burden on the society, healthcare system, insurance system, and the patients themselves. Therefore, it is suggested that health policymakers and managers should take appropriate measures to increase the basic and supplemental insurance coverage of these patients. In addition, in order to reduce the costs, proper and equitable distribution of psychiatrists and psychiatric beds, expansion of home care services, and use of Internet-based technologies and the cyberspace to follow up the treatment of these patients are recommended.
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