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Understanding differences in terms of clinical phenotypes and outcomes of coronavirus disease 2019 (COVID-19) compared with influenza is vital to optimizing the management of patients and planning healthcare. Herein, we aimed to investigate the clinical differences and outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza. We performed a retrospective study of hospitalized children who were positive for SARS-CoV-2 between March 2020 and March 2021 and for influenza between January 2016 and February 2020 in respiratory samples. The primary outcome of this study was pediatric intensive care unit (PICU) admission, and the secondary outcome was the need for respiratory support. A total of 74 patients with influenza and 71 who were positive for SARS-CoV-2 were included. The distribution among the sexes was similar, but patients with COVID-19 were older than patients with influenza (96 vs. 12, p < 0.001). In terms of underlying chronic diseases, the frequency was 26.7% in the COVID-19 group and 54% in the influenza group (p = 0.001). The comparison of symptoms revealed that fatigue, headache, nausea, vomiting, and abdominal pain occurred more frequently with COVID-19 (for all p < 0.05) and runny nose with influenza (p = 0.002). The frequency of admission to the PICU was relatively higher (18.9%) in the influenza group than with COVID-19 (2.8%) with a significant ratio (p = 0.001), secondary bacterial infections were observed more frequently in the influenza group (20.2% vs. 4.2%, p = 0.003). Some 88.7% of patients with COVID-19 did not need respiratory support, whereas 59.4% of patients with influenza did require respiratory support (p < 0.001). This study noted that influenza caused more frequent admissions to the PICU and a greater need for respiratory support in hospitalized pediatric patients than COVID-19., (© 2022 Wiley Periodicals LLC.)