The predominant organic system involved in multisystem inflammatory syndrome in children associated with COVID-19 is the gastrointestinal system, which is observed in almost 90% of patients. Gastrointestinal symptoms can mimic acute appendicitis. There have been a few cases of misdiagnosed multisystem inflammatory syndrome in children associated with SARS-CoV-2 as appendicitis, and a few concomitant cases of a multisystem inflammatory syndrome associated with acute appendicitis during the COVID-19 pandemic. Here, we present the case of an 11-year-old girl who presented to our Intensive Care Unit with a 2-day history of fever, generalized abdominal pain, and vomiting. The clinical findings resulted in a clinical suspicion of acute appendicitis and subsequent surgery. While postoperatively, she became critically ill, and she was diagnosed with the multisystem inflammatory syndrome in children associated with COVID-19. When diagnosing children with acute appendicitis, healthcare professionals, especially pediatricians and surgeons, must pay attention to the multisystem inflammatory syndrome linked to the SARS-CoV-2 infection.