Objectives/HypothesisTo assess the efficacy of 0.23% povidone-iodine (PVP-I) nasal rinses and mouth washes on detectability of the coronavirus disease 2019 (COVID-19) virus and cycle threshold (Ct) values in nasopharyngeal swabs.Study designThis was an open-label, prospective, randomized, placebo-controlled clinical trial.SettingThe study was conducted in King Saud University Medical City, Riyadh, Saudi Arabia, from August 2021 to July 2022.MethodsParticipants diagnosed with SARS-CoV-2 were randomly assigned to one of three groups, with participants receiving either 0.23% PVP-I, 0.9% normal saline (NS) nasal rinses and mouth washes, or no intervention (control group). Nasopharyngeal swabs were taken 4, 8, 12, and 18 days after the first swab to measure the detectability of the virus and the Ct.ResultsA total of 19 participants were involved in this study. The mean viral survival was 9.8, 12, and 12.6 days for the PVP-I, NS, and control groups, respectively, with a statistically significant difference (p = 0.046). The Ct mean values were 23 ± 3.4, 23.5 ± 6.3, and 26.3 ± 5.9 at the time of recruitment and 25.2 ± 3.5, 15 ± 11.7, and 26.9 ± 6.4 after 4 days for the PVP-I, NS, and control groups, respectively.ConclusionsWhen used continuously at a concentration of 0.23%, PVP-I showed promising results in terms of decreasing the pandemic burden by reducing the period of infectiousness and viral load. However, the use of PVP-I did not result in significantly different changes in the quality-of-life parameters in recently vaccinated and mild COVID-19 patients.