ObjectivesMonoclonal antibodies can slow COVID-19 progression. This study describes the experience of using sotrovimab in patients with COVID-19 at high risk for disease progression and hospitalisation within the United Arab Emirates (UAE).DesignObservational cohort study.SettingA tertiary hospital in the Emirate of Sharjah, UAE.ParticipantsPatients with mild or moderate COVID-19 at high risk for disease progression.InterventionsInfusion with a single 500 mg dose of the monoclonal antibody drug sotrovimab.Primary and secondary outcome measuresAny adverse effect within 24 hours, disease progression within 5 days, emergency department visit within 10 days, hospital admission within 10 days or mortality within 28 days of infusion.Results3227 high-risk COVID-19 patients were infused with sotrovimab during the mild (n=3107, 96.3%) or moderate (n=120, 3.7%) disease stages. The incidence of at least one outcome was recorded in 196 (6.1%) of the patients (60.7 per 1000 patients). The most common outcome was disease progression within 5 days of infusion in 129 patients (4.0%), followed by emergency department visits by 90 patients (2.8%) within 10 days. Twenty-nine (0.9%) patients were hospitalised within 10 days of infusion with only two deaths (0.1%). Patients infused with sotrovimab during the moderate disease stage had 11 times greater odds of developing at least one outcome compared with patients infused during the mild stage (adjusted OR, aOR 10.86, 95% CI 7.14 to 16.54). SARS-CoV-2 vaccinated (aOR 12.8, 95% CI 7.3 to 20.5) and unvaccinated (aOR 7.2, 95% CI 3.4 to 15.3) patients infused with sotrovimab during the moderate disease stage had similar odds of at least one outcome compared with patients infused during the mild stage.ConclusionsAmong high-risk sotrovimab-infused COVID-19 patients, there were relatively low incidences of disease progression and hospitalisation. Regardless of vaccination history, monoclonal antibody intervention during the early stages of COVID-19 results in better outcomes.