The efficacy of pre-exposure prophylaxis by the Tixagevimab/Cilgavimab cocktail (AZD7442) was evaluated in hamsters against a clinical BA.1 strain of SARS-CoV-2 variant Omicron. AZD7442 retains inhibitory activity against Omicron despite a substantial loss of efficacy. We estimate that Omicron virus requires about 20-times more antibodies in plasma than the ancestral B.1 strain (G614) virus to achieve a similar drug efficacy in reducing lung infectious titers.