Financial protection of populations against healthcare costs is one of the fundamental responsibilities of governments. This study aimed to investigate the incidence of catastrophic health expenditures (CHE) and it's affecting factors in hospitalized patients with delta variant of COVID-19. In this cross-sectional study, we included 400 hospitalized COVID-19 patients at Kosar Hospital of Semnan in 2022, using a researcher-made checklist. Based on qualitative nature of the variables, chi-square test was used to investigate the statistical associations between the demographic/background characteristics and the incidence of CHE. On average, COVID-19 imposed 1833.43 USD direct medical costs per one hospitalized patient. The ratio of direct-medical costs to household's non-food expenses was 2.35, and 61% (CI:±4.78%) of the patients were subject to CHE. Besides, residence place, basic insurance type, benefitting from supplementary insurance, suffering from underlying diseases, hospitalization in ICU, falling into a coma, facing pulmonary failure, and performing hemoperfusion had significant associations with CHE ( <0.05). The incidence of CHE in hospitalized COVID-19 patients was undesirable, which may be due to geographical, economical, and occupational inequalities apart from the factors related to the severity of the disease. So, health policymakers should pay attention to the provision of proper financial risk protection policies to make the health insurance system more efficient and appropriate.