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Background: In Japan, medical expenses for COVID-19 treatment transitioned from full public funding support to out-of-pocket (OOP) payment by patients plus partial public support in October 2023, and public support fully ended in March 2024. This study evaluated the clinical and economic impacts of initiating OOP payments., Research Design and Methods: To assess the impact on prescription rates, we compared the prescription rates of antivirals from the 4-month pre- to post-OOP payment initiation period using a claims database. Subsequently, a budget impact model assessed the impacts of a hypothetical decline in the prescription rates on COVID-19-related hospitalizations, deaths, and direct medical costs for antiviral prescription and hospitalization., Results: The antiviral prescription rate per 100 patients decreased from 17.5 for the pre-OOP payment initiation period to 11.5 for the post-OOP payment initiation period, that is, a change of - 34.3%. With prescription rate decreases of 40%, 60%, and 80%, the hospitalizations would increase annually by 22,533 (3.3%), 33800 (5.0%), and 45,066 (6.6%), respectively. The total costs would increase by JPY9.5 billion (USD67.3 million; 0.7%), JPY14.3 billion (USD100.9 million; 1.0%), and JPY19.0 billion (USD134.5 million; 1.3%), respectively., Conclusions: Higher OOP payment decreased the antiviral prescription rate, potentially leading to clinical and economic loss.