Abstract Aim This study aims to assess rates of antibiotic prescriptions and its determinants in in children with COVID‐19 or Multisystem Inflammatory Syndrome (MIS‐C). Methods Children <18 years‐old assessed in five Latin Americas countries with a diagnosis of COVID‐19 or MIS‐C were enrolled. Antibiotic prescriptions and factors associated with their use were assessed. Results A total of 990 children were included: 921 (93%) with COVID‐19, 69 (7.0%) with MIS‐C. The prevalence of antibiotic use was 24.5% ( n = 243). MIS‐C with (OR = 45.48) or without (OR = 10.35) cardiac involvement, provision of intensive care (OR = 9.60), need for hospital care (OR = 6.87), pneumonia and/or ARDS detected through chest X‐rays (OR = 4.40), administration of systemic corticosteroids (OR = 4.39), oxygen support, mechanical ventilation or CPAP (OR = 2.21), pyrexia (OR = 1.84), and female sex (OR = 1.50) were independently associated with increased use of antibiotics. There was significant variation in antibiotic use across the hospitals. Conclusion Our study showed a high rate of antibiotic prescriptions in children with COVID‐19, in particular in those with severe disease or MIS‐C. Prospective studies are needed to provide better evidence on the recognition and management of bacterial infections in COVID‐19 children.