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Introduction: Although patients’ clinical conditions have been shown to be associated with coronavirus disease (COVID-19) severity and outcome, their impact on hospital costs are not known. This economic evaluation of COVID-19 admissions aimed to assess direct and fixed hospital costs and describe their particularities in different clinical and demographic conditions and outcomes in the largest public hospital in Latin America, located in São Paulo, Brazil, where a whole institute was exclusively dedicated to COVID-19 patients in response to the pandemic. Methods: This is a partial economic evaluation performed from the hospital´s perspective and is a prospective, observational cohort study to assess hospitalization costs of suspected and confirmed COVID-19 patients admitted between March 30 and June 30, 2020, to Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP) and followed until discharge, death, or external transfer. Micro- and macro-costing methodologies were used to describe and analyze the total cost associated with each patient's underlying medical conditions, itinerary and outcomes as well as the cost components of different hospital sectors. Results: The average cost of the 3254 admissions (51.7% of which involved intensive care unit stays) was US$12,637.42. The overhead cost was its main component. Sex, age and underlying hypertension (US$14,746.77), diabetes (US$15,002.12), obesity (US$18,941.55), chronic renal failure (US$15,377.84), and rheumatic (US$17,764.61), hematologic (US$15,908.25) and neurologic (US$15,257.95) diseases were associated with higher costs. Age strata >69 years, reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19, comorbidities, use of mechanical ventilation or dialysis, surgery and outcomes remained associated with higher costs. Conclusion: Knowledge of COVID-19 hospital costs can aid in the development of a comprehensive approach for decision-making and planning for future risk management.