The COVID-19 pandemic is a global crisis that has continued to impact health, population, and the economy. Therefore, this study aims to evaluate the cost-effectiveness of COVID-19 treatment for hospitalized patients from the perspective of healthcare providers. An observational study was conducted retrospectively by collecting data from medical records of hospitalized COVID-19 patients between April 1 and June 30, 2021. The effectiveness of the therapy was evaluated based on COVID-19 treatment guidelines in Indonesia, by calculating the number of recovered patients within 14 days. The study only considered the direct medical costs of treatment, while the cost-effectiveness was analyzed using Average Cost-Effectiveness Ratio (ACER) and Incremental Cost-Effectiveness Ratio (ICER). The results showed that the average direct cost of COVID-19 treatment per patient was approximately IDR 28,114,775.52 ± IDR 16,352,597.11. The most effective treatment was Favipiravir + Levofloxacin + N-acetylcysteine, followed by Favipiravir + Levofloxacin + Azithromycin + N-acetylcysteine, with 97% and 91% effectiveness, respectively. The ACER of COVID-19 treatments ranged from Rp 15,596,973 to 58,140,864, while the ICER was mainly located in the South East Quadrant, with Favipiravir + Levofloxacin + N-acetylcysteine being dominant compared to other treatments, saving IDR 161,653.97 to 33,870,916.17 per recovered patient. Effective COVID-19 treatments for hospitalized patients provide good value for the health system. However, this study was limited by the unavailability of the most recent information on the rapidly evolving pandemic.