BACKGROUND: To date, there are no comprehensive data on pediatric COVID-19 from Latin America. This study aims to assess COVID-19 and Multisystem Inflammatory Syndrome (MIS-C) in Latin American children, to appropriately plan and allocate resources to face the pandemic on a local and international level. METHODS: Ambispective multicenter cohort study from 5 Latin American countries. Children 18 years of age or younger with microbiologically confirmed SARS-CoV-2 infection or fulfilling MIS-C definition were included. FINDINGS: Four hundred nine children were included, with a median age of 3.0 years (interquartile range 0.6-9.0). Of these, 95 (23.2%) were diagnosed with MIS-C. One hundred ninety-one (46.7%) children were admitted to hospital and 52 (12.7%) required admission to a pediatric intensive care unit. Ninety-two (22.5%) patients required oxygen support: 8 (2%) were started on continuous positive airway pressure and 29 (7%) on mechanical ventilation. Thirty-five (8.5%) patients required inotropic support. The following factors were associated with pediatric intensive care unit admission: preexisting medical condition (P < 0.0001), immunodeficiency (P = 0.01), lower respiratory tract infection (P < 0.0001), gastrointestinal symptoms (P = 0.006), radiologic changes suggestive of pneumonia and acute respiratory distress syndrome (P < 0.0001) and low socioeconomic conditions (P = 0.009). CONCLUSIONS: This study shows a generally more severe form of COVID-19 and a high number of MIS-C in Latin American children, compared with studies from China, Europe and North America, and support current evidence of a more severe disease in Latin/Hispanic children or in people of lower socioeconomic level. The findings highlight an urgent need for more data on COVID-19 in Latin America.