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Background Antibodies targeting envelope glycoproteins have been shown in some instances to enhance infection by subverting Fc receptor and complement function, or by directly inducing fusion with cellular membranes. The potential for antibody dependent enhancement (ADE) of infection raises concern that passive immunization with a therapeutic anti-viral antibody could increase risk of disease. As part of the nonclinical package characterizing the risk profile of the SARS-CoV-2 neutralizing monoclonal antibody bamlanivimab, studies were conducted to evaluate the potential for ADE of infection in vitro and in a non-human primate model of COVID-19. Methods In vitro assays were performed in primary human macrophage, Raji, or THP-1 cells exposed to SARS-CoV-2 in the presence of bamlanivimab ranging from approximately IC50 to more than 100-fold above or below the IC50. Samples were evaluated for demonstration of productive viral infection. Bamlanivimab binding to C1q and FcR were quantified, and activity was studied by cell-based assays. In vivo studies were performed in African green monkeys (AGM) infected with SARS-CoV-2 virus following sub-saturating or saturating doses of bamlanivimab or IgG control. Viral loads, clinical pathology, and histology endpoints were assessed to determine if bamlanivimab enhanced SARS-CoV-2 replication or clinical illness. Mixed model repeated measures were used to evaluate virology statistics. Results Bamlanivimab did not increase viral RNA production in FcγR-expressing cell lines, despite demonstration of effector function. No significant differences were found among the AGM groups in terms of weight, temperature, or food intake. Treatment with bamlanivimab reduced viral loads in nasal and oral swabs and BAL fluid relative to control groups. Viral antigen was not detected in lung tissue from animals treated with the highest dose of bamlanivimab. Microscopic findings along with decreases in viral loads in bamlanivimab-treated animals indicated that ADE of disease was not observed in this study. Conclusions Sub-saturating doses of bamlanivimab treatment do not induce ADE of SARSCoV2 infection in either in vitro or an AGM model of infection. Findings suggest that high affinity monoclonal antibodies pose a low risk of mediating ADE in patients and further supports their safety profile as a treatment of COVID-19 disease.