Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is a rare life-threatening clinical condition that can develop in patients younger than 21 years of age with a history of infection/exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The cardiovascular system is a main target of the inflammatory process that frequently causes myocardial dysfunction, myopericarditis, coronary artery dilation, hypotension, and shock. Multisystem inflammatory syndrome in children-associated myocarditis is usually characterized by fever, tachycardia, non-specific electrocardiogram abnormalities, and left ventricular dysfunction, but serious tachyarrhythmias may also occur. We report two cases of patients with MIS-C-associated myocarditis who developed severe bradycardia. Case summary Two female adolescents with recent history of coronavirus disease 2019 (COVID-19) were initially hospitalized for long-lasting high-grade fever and severe gastrointestinal symptoms. Both patients were diagnosed with MIS-C-associated myocarditis for elevation of markers of myocardial injury (mean highly-sensitive cardiac troponin 2663 pg/mL, mean N-terminal-pro-brain natriuretic peptide 5097 pg/mL) and left ventricular dysfunction, which was subsequently confirmed by cardiac magnetic resonance. Both patients developed a severe sinus bradycardia (lowest heart rate 36 and 42, respectively), which appeared refractory to the treatment with intravenous Methylprednisolone and Immunoglobulins, despite a clinical and biochemical improvement. The use of Anakinra (a recombinant interleukin-1 receptor antagonist), was associated with a rapid improvement of cardiac rhythm and excellent clinical outcome at 6 months of follow-up. Discussion In patients with MIS-C-associated myocarditis, a continuous cardiac monitoring is mandatory to promptly identify potential conduction abnormalities. Adolescents may present bradycardia as a rhythm complication. We experienced a rapid recovery after treatment with Anakinra, to be considered as add-on therapy in cases refractory to standard anti-inflammatory treatment.