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Abstract The economic impact of the COVID-19 pandemic on global health systems is a major concern. To plan and allocate resources to treat COVID-19 patients and provide insights into the financial sustainability of healthcare systems in fighting the future pandemic, measuring the costs to treat COVID-19 patients is deemed necessary. As such, we conducted a retrospective, real-world observational study to measure the direct medical cost of treating COVID-19 patients at a tertiary care hospital in Saudi Arabia. The analysis was conducted using primary data and a mixed methodology of micro and macro-costing. Between July 2020 and July 2021, 287 patients with confirmed COVID-19 were admitted and their data were analyzed. COVID-19 infection was confirmed by RT-PCR or serologic tests in all the included patients. There were 60 cases of mild to moderate disease, 148 cases of severe disease, and 79 critically ill patients. The cost per case for mild to moderate disease, severe disease, and critically ill was 2003 USD, 14,545 USD, and 20,188 USD, respectively. There was a statistically significant difference in the cost between patients with comorbidities and patients without comorbidities (P-value 0.008). Across patients with and without comorbidities, there was a significant difference in the cost of the bed, laboratory work, treatment medications, and non-pharmaceutical equipment. The cost of treating COVID-19 patients is considered a burden for many countries. More studies from different private and governmental hospitals are needed to compare different study findings for better preparation for the current COVID-19 as well as future pandemics.