Down syndrome is the most common human chromosomal disorder. Whether Down syndrome is a risk factor for severe COVID-19 outcomes in pediatric patients remains unclear, especially in low-to-middle income countries. We gathered data on patients <18 years of age with SARS-CoV-2 infection from a national registry in Brazil to assess the risk for severe outcomes among patients with Down syndrome. We included data from 14,684 hospitalized patients, 261 of whom had Down syndrome. After adjustments for sociodemographic and medical factors, patients with Down syndrome had 1.8 times higher odds of dying from COVID-19 (odds ratio 1.82, 95% CI 1.22-2.68) and 27% longer recovery times (hazard ratio 0.73, 95% CI 0.61-0.86) than patients without Down syndrome. We found Down syndrome was associated with increased risk for severe illness and death among COVID-19 patients. Guidelines for managing COVID-19 among pediatric patients with Down syndrome could improve outcomes for this population.