Background: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was detected in the psychiatric ward of a general hospital in Brasília, Brazil. Methods: We report the investigation, clinical outcomes, viral sequencing, and control measures applied to outbreak containment. Results: The overall attack rate was 95% (23/24) in a period of 13 days. Among the cases, 78% (18/23) were vaccinated and 17% (4/23) required intensive care. The Omicron variant was isolated from the 19 sequenced samples. Conclusions: The findings highlight the potential harm that highly transmissible variants may generate among hospitalized populations, particularly those with comorbidities.