This study evaluates the effect of molnupiravir on clinical improvement, viral clearance and antibody responses of COVID-19 patients who previously developed immunity through vaccination or prior infection. This multi-center, prospective, observational study included all mild adult COVID-19 cases for whom molnupiravir was recommended during the study period. The primary outcome was hospitalization, death or new oxygen need due to COVID-19 within 28 days of follow-up. The effects of molnupiravir on viral clearance, serum biochemical tests and SARS-CoV-2 antibody levels were also assessed. A total of 844 patients (402 molnupiravir, 442 no molnupiravir) were included. The mean age was 66, 75% of them were vaccinated. The primary outcome occurred in 8 patients, with no significant difference different between propensity score-matched groups. Molnupiravir showed no effect on clinical improvement. Viral clearance was higher in the molnupiravir group on day 3, but higher in the untreated group by day 10. Serum SARS-CoV-2 antibody levels on day 28 were lower in the molnupiravir group. The effectiveness of molnupiravir in reducing hospitalization and death may be insufficient in previously immune COVID-19 patients. Additionally, molnupiravir may reduce day-28 serum SARS-CoV-2 antibody level.