Objectives: To determine if commercially available mouthwash with b-cyclodextrin and citrox (bio- flavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load. Methods: In this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) PCR-positive patients aged 18e85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2. Results: The intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log10 copies/mL) decrease T1eT2 of e12.58% (IQR e29.55% to e0.16%). The second dose maintained the low median value for the CDCM (3.08 log10 copies/mL; IQR 0e4.19), compared with placebo (3.31 log10 copies/mL; IQR 1.18e4.75). At day 7, there was still a greater median percentage (log10 copies/mL) decrease in salivary viral load over time in the CDCM group (e58.62%; IQR e100% to e34.36%) compared with the placebo group (e50.62%; IQR e100% to e27.66%). These results were confirmed by the per-protocol analysis. Conclusions: This trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.