OBJECTIVES: To characterize the COVID-19 disease profile in Chilean children hospitalized in pediatric intensive care units (PICU) and to evaluate risk factors associated with severe COVID-19. PATIENTS AND METHOD: A multicenter prospective cohort study with patients 0-18 years of age with confirmed SARS-CoV-2 hospitalized in PICU. Clinical, laboratory, imaging, and therapeutic variables were recorded. We compared "mild/moderate COVID-19" with ''severe COVID-19" using median with interquartile range (IQR), Mann-Whitney U test, two-tailed Fisher's test, and forward binary multivariate analysis to adjust variables for "severe COVID-19". A p < 0.05 was considered significant. RESULTS: From 16 PICUs, 219 patients were recruited, 55.3% were male, with a median age of 86 months (IQR: 13.5-156). The most frequent comorbidities were obesity and respiratory diseases. Overall mortality was 3.6%. "Severe COVID-19" (26.5%) showed more leukopenia, lymphopenia, increased inflammatory parameters, and altered organ function (p < 0.05). It also developed more sepsis/shock, ARDS, and organ dysfunction, requiring more hemodynamic, anti-inflammatory, anticoagulation, and antibiotic therapy, with a longer stay in the PICU/hospital (p < 0.05), and 13.8% of mortality. Risk factors associated with "severe COVID-19" were shock on admission to the PICU [aOR 28.44 (95%CI 10.45-77.4)], obesity [aOR 3.55 (95%CI 1.3-9.6)], consolidation [aOR 3.1 (95%CI 1.1 -8.7)], atelectasis [aOR: 8.7 (95%CI 1.17-64.3)], stress dose of corticosteroids [aOR 7.7 (95%CI 1.9-30.6)], early antibiotic therapy [aOR: 12.02 (95%CI 1.11-130.02)], acquired/congenital immunodeficiency [aOR: 19.2 (95%CI: 1.19-321)], and oncological pathology [aOR 10.7 (95%CI 2.14-47.8)]. CONCLUSION: In this Chilean pediatric cohort, most patients with COVID-19 admitted to de PICU were male, of school age, with associated comorbidity. Risk factors for developing severe COVID-19 were the presence of comorbidities such as acquired/congenital immunodeficiency, oncological pathology, and obesity, in addition to shock on admission and consolidations on X-rays.