Introduction: Immune dysregulation happens after exposure to corona virus disease-2019 (COVID-19) and affects many organs. It is confirmed with a positive COVID-19 test history, fever, and the involvement of 2 or more organs, but it is hard to diagnose in neonates. Case Presentation: There were 2 Persian neonates admitted to the Neonatal Intensive Care Unit or neonatal ward of the Children’s Medical Center, Tehran, Iran, with sepsis in this case presentation. The trunk and extremities were affected by macular rashes in both cases. COVID-19 tests in both cases were negative, but both of their mothers were affected by COVID-19 before delivery. In both cases, systemic and macular rashes responded to corticosteroids. Conclusions: Macular rash can present multisystem inflammatory disease in neonates. Neonates with a positive history of COVID-19 in parents or relatives should be considered for this syndrome.