BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has imposed significant burden on Brazil's health system. This study aimed to examine clinical characteristics, overall vaccine uptake, and to assess healthcare resource utilization (HCRU) and costs associated with acute COVID-19 in Brazil during the Omicron predominant period. METHODS: A nationwide retrospective study was conducted using various Brazilian databases including, COVID-19 related databases, public health systems, and other surveillance/demographic datasets. Individuals with positive COVID-19 test results between January 1 2022 and April 30 2022, during Omicron BA.1/BA.2 wave, were identified. Patients' demographics, vaccine uptake, HCRU and corresponding costs were described by age groups. RESULTS: A total of 8,160,715 (3.80%) COVID-19 cases were identified in the study cohort, ranging from 2.43% in <5 years to 62.05% in 19-49 years. The uptake of partial (Dose 1) or full immunization (Dose 2) was less than 0.1% in children aged <5 years, whereas in individuals ≥ 19 years, it exceeded 89.78% for Dose 1 and 84.07% for Dose 2. Overall booster vaccine uptake was 38.06%, which was significantly higher among individuals aged ≥ 65 years, surpassing 74.79%. Regardless of vaccination status, 87.2% cases were symptomatic, and 1.48% were hospitalized due to acute COVID-19 (<5 years: 2.33%, 5-11 years: 0.99%, 12-18 years: 0.32%, 19-49 years: 0.40%; 50-64 years: 1.50%, 65-74 years: 5.43%, and ≥ 75 years: 17.89%). Among the hospitalized patients (n = 120,450), 32.57% were admitted to ICU, of whom 31,283 (79.75%) individuals required mechanical ventilation (MV) support. The average cost per day in normal ward and ICU without MV in public/general hospital settings was $104.36 and $302.81, respectively. While average cost per day in normal ward and ICU with MV was $75.91 and $301.22 respectively. CONCLUSIONS: This study quantified the burden of COVID-19 in Brazil, suggesting substantial healthcare resources required to manage the COVID-19 pandemic.