Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe manifestation of coronavirus disease 2019 (COVID-19). The aim of this study was to describe the characteristics of children with MIS-C admitted to a pediatric tertiary hospital in Portugal.Material and Methods: Observational descriptive study of MIS-C patients admitted between April 2020 and April 2021. Demographic and clinical characteristics, diagnostic tests, and treatment data were collected. The diagnosis of MIS-C was based on the World Health Organization and Centers for Disease Control and Prevention criteria.Results: We reported 45 children with MIS-C. The median age was seven years (IQR 4 - 10 years) and 60.0% were previously healthy. SARS-CoV-2 infection was confirmed in 77.8% by RT-PCR or antibody testing for SARS-CoV-2, and in 73.3%, an epidemiological link was confirmed. All the patients had a fever and organ system involvement: hematologic (100%), cardiovascular (97.8%), gastrointestinal (97.8%), mucocutaneous (86.7%), respiratory (26.7%), neurologic (15.6%), and renal (13.3%) system. Neurological (p = 0.035) and respiratory (p = 0.035) involvement were observed in patients with a more severe presentation. There was a significant difference of medians when comparing disease severity groups, namely in the values of hemoglobin (p = 0.015), lymphocytes (p = 0.030), D-dimer (p = 0.019), albumin (p < 0.001), NT-proBNP (p = 0.005), ferritin (p = 0.048), CRP (p = 0.006), procalcitonin (p = 0.005) and IL-6 (p = 0.002). From the total number of children, 93.3% received intravenous immunoglobulin, 91.1% methylprednisolone, and one patient (2.2%) received anakinra. Thirteen patients (28.8%) required intensive care and there were no deaths. Of the 21 patients evaluated, 90.4% had reduction of exercise capacity and of the 15 patients who underwent cardiac magnetic resonance, 53.3% had sequelae of cardiac injury.Conclusion: We observed a large spectrum of disease presentation in a group of patients where most were previously healthy. A small percentage of patients (28.9%) had a severe presentation of the disease. MIS-C is a challenge in current clinical practice and its diagnosis requires a high level of clinical suspicion as the timely initiation of therapy is essential to prevent complications. However, there is no scientific consensus on the treatment and follow-up of these patients.