The SARS-COV-2 virus is the cause of COVID-19, a disease that has spread to many countries. The COVID-19 Management Guidelines in Indonesia include azithromycin as one of the antibiotics used to treat COVID-19. Antibiotics are needed in patients with possible co-infection. This study aimed to determine the potential drug interaction of azithromycin with other therapy in hospitalized COVID-19 patients at the Banyumas Regional General Hospital. The study was descriptive observational research. The data was collected retrospectively based on medical records of hospitalized COVID-19 patients at the Banyumas Regional General Hospital from July 2020 to June 2021. The Lexi-Interact™ and Drugbank online is used to identify potential drug interactions. A total of 221 patients were included, with 122 patients (55.21%) being women. The number of patients experiencing potential-drug interactions was 199 patients (90%), with a number of potential drug interactions were 289 cases. The most potential drug interaction was azithromycin with omeprazole (85 cases - 29.41%). Most cases were moderate severity with pharmacokinetic interaction. This study concluded that the administration of azithromycin with other drugs for COVID-19 patients at the Banyumas Hospital has the potential for interactions that could be prevented by monitoring related side effects.