Treatment of infectious disease with single monoclonal antibodies (mAbs) can exert a selective pressure that potentially increases the possibility of mutational escape of the targeted antigen. This risk can be reduced through the combination of multiple mAbs targeting non-overlapping epitopes. In this preprint, Baum et al. show the protective effects of REGN-COV2, a cocktail of two fully humanized mAbs that bind to different regions of the SARS-CoV-2 spike protein. Rhesus macaques and golden hamsters treated with REGN-COV2 have markedly lower levels of detectable sub-genomic viral mRNA in both prophylactic and therapeutic settings. In rhesus macaques, the mRNA decrease is evident in oral and nasopharyngeal swabs, as well as in bronchoalveolar lavage. Combined-phase clinical trials for REGN-COV2 are underway.