Background: Multisystem inflammatory syndrome of children (MIS-C) has emerged as a serious systemic inflammatory disorder complicating COVID-19 infection in children. Arterial and venous thrombosis have been reported complicating COVID-19 infection but not infective endocarditis (IE). Case presentation: Herein, we describe a 12-year-old girl initially presented with picture of MIS-C with echocardiography (ECHO) revealing only pericardial effusion, for which she has received single dose of pulsed methylprednisolone with no improvement, her blood picture was significant for anemia and thrombocytopenia, with increased acute phase reactants (APRs) including serum ferritin and IL-6. She was found to have as well oral ulcers, polyarthritis, vascular purpura, and exaggerated deep tendon reflexes. She had history of low-grade fever, gastrointestinal illness, together with myalgia and easily fatigability during the last month before presentation, symptoms suggestive of viral infection most probably SARS-CoV-2 infection with positive COVID-19 IgG. The girl was considered as probable systemic lupus erythematosus (SLE) in face of negative immunological evaluation for SLE except for moderately positive anti-cardiolipin IgM. Initially, the girl has responded to intravenous steroids but ten days later, she came back toxic with marked increase in APRs and ECHO revealed left atrial mural highly mobile floating mass, blood culture was positive for staphylococcus coagulase negative organism, steroids were gradually withdrawn, and complete resolution of the IE was achieved after six weeks of parenteral antibiotics. Conclusion: COVID-19 infection can result in subclinical cardiac affection making the heart vulnerable to colonization with even mild bacteremia. Although autoimmune features of IE are uncommon but can confuse the presentation especially when the vegetations could not initially be detected by ECHO.