ABSTRACT Evaluating the antiviral potential of widely available commercial antiseptic rinses on SARS-CoV-2 infectivity holds great potential for rapidly reducing viral transmission, particularly as novel strains emerge. Given that SARS- CoV-2 is transmitted primarily through aerosols and salivary and respiratory secretions, strategies to reduce viral burden is an attractive approach to mitigating spread; this is particularly true for dental and other healthcare settings which have high patient volumes, require work in close proximity to the head and neck, and generate procedural aerosols. Though studies have demonstrated that some antiseptic mouth rinses have antiviral properties against SARS-CoV-2 in vitro and other enveloped viruses in vivo, data are still emerging from recent randomized clinical trials (RCT), including ours at the Adams School of Dentistry, regarding whether antiseptic mouth rinses reduce SARS-CoV-2 in vivo. To address this gap in knowledge, we propose to determine whether mouth rinses containing ethanol, hydrogen peroxide, povidone-iodine, chlorhexidine, or cetylpyridinium chloride reduce SARS-CoV-2 viral load, replication and infectivity (Aim 1) and to characterize salivary inflammatory and antibody responses associated with early SARS-CoV-2 infection (Aim 2) using salivary samples derived from our recent COVID-19+ patient RCT. Altogether, the data generated from these aims will demonstrate whether antiseptic rinses reduce salivary SARS-CoV-2 viral load and infectivity, and will characterize the local inflammatory response to SARS-CoV-2 in the oral cavity with the ultimate goal of limiting viral spread. These studies will generate data to develop feasible, inexpensive, rapidly implementable protocols to mitigate the spread of SARS-CoV-2 and address this urgent public health need with broad translational impact. Our interdisciplinary team is uniquely qualified to conduct the proposed work as we have the innovative methodologies, BLS2+ facilities, SARS-CoV-2+ samples, and expertise to achieve our aims. This application includes collaboration between experienced and junior faculty across multiple disciplines to ensure the rigor and translatability of our findings.