Sotrovimab, an antibody active against severe acute respiratory syndrome coronavirus 2 that neutralizes antibodies, reduced the risk of COVID-19-related hospitalization or death in studies conducted before the emergence of the Omicron variant. The objective of this study is to evaluate the clinical efficacy of sotrovimab in patients with mild to moderate COVID-19 Omicron BA.1 and BA.2 subvariant infections using a propensity score matching method. The propensity score-matched cohort study population was derived from patients who received sotrovimab. We derived a comparator group from an age- and sex-matched population who were recuperating in a medical facility after COVID-19 infection or from elderly person entrance facilities during the same period who were eligible for but did not receive sotrovimab treatment. In total, 642 patients in the BA.1 subvariant group and 202 in the BA.2 subvariant group and matched individuals were analyzed. The outcome was the requirement for oxygen therapy. In the treatment group, 26 patients with the BA.1 subvariant and 8 patients with the BA.2 subvariant received oxygen therapy. The administration of oxygen therapy was significantly lower in the treatment group than in the control group (BA.1 subvariant group, 4.0% vs. 8.7%,p= 0.0008; BA.2 subvariant group, 4.0% vs. 9.9%,p= 0.0296). All these patients were admitted to our hospitals and received additional therapy and then recovered. No deaths were observed in either group. Our results demonstrate that the sotrovimab antibody treatment may be associated with a reduction in the requirement for oxygen therapy among high-risk patients with mild to moderate COVID-19 Omicron BA.1 and BA.2 subvariants.