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Introduction: Suppression of tumorigenicity 2 (ST2) plays a key role in the serious complications that may occur during Coronavirus disease-2019 (COVID-19), including systemic inflammatory condition, sepsis, Acute respiratory distress syndrome, and fibrosis. In this study, we evaluated the relationship between the serum ST2 concentrations and the mortality and need for mechanical ventilation. Materials and Methods: A prospective observational study was conducted in patients diagnosed with COVID-19 who presented to the emergency department (ED) between October 2021 and April 2022. Patients with Severe acute respiratory syndrome-Coronavirus-2 infection were consecutively enrolled according to the clinical spectrum defined in the guidelines. Admission to the intensive care unit (ICU), requirement of intubation, and 90-day mortality were the primary study outcomes. Clinical, imaging and laboratory data were assessed to determine the clinical spectrum and severity scores. ST2 was assessed using the micro ELISA method and Sandwich-ELISA principle. Results: Of the 64 (48.5%) patients admitted to the ICU, 43 (32.6%) required mechanical ventilation. During the 90-day follow-up period, 44 (33.3%) patients died due to clinical deterioration. The median ST2 concentration at admission was 272.5 ng/mL in patients who died and 55.95 ng/mL in patients who survived (p