Patient: Female, newborn Final Diagnosis: Primary hemophagocytic lymphohistiocytosis (HLH) Symptoms: Fever • poor feeding • respiratory distress Medication: — Clinical Procedure: — Specialty: Hematology • Pediatrics and Neonatology Objective: Rare disease Background: Infants born to mothers with Coronavirus disease (COVID-19) are susceptible to infection, either vertically or horizontally. The mechanism is not completely understood. Regardless, it is rare that an infant with COVID-19 suffers from serious, life-threatening complications. We speculate that one of these complications can be hemophagocytic lymphohistiocytosis (HLH), a dysregulated hyperinflammatory response that leads to multi-organ failure. Case Report: We describe a case of a female newborn, born to a SARS-CoV-2-positive mother via cesarean section delivery at 35 weeks of gestation, that tested positive for SARS-CoV-2 on the first day after birth. The patient presented with progressive respiratory distress, intermittent fever, splenomegaly, and cytopenia. Hemophagocytic lymphohistiocytosis (HLH) work-up was done, which showed hyperferritinemia, hypofibrinogenemia, and hyper-triglyceridemia. Bone marrow aspirate showed hemophagocytic activity of both red blood cells and platelets. We suspect that the virus triggered HLH, which led to the patient’s death at 51 days of age due to severe respiratory failure. Conclusion: Infants and children suffer from milder symptoms than adults when infected with SARS-CoV-2, for reasons not well understood, although multiple hypotheses have been proposed, which are discussed in this paper. However, there is a possibility that the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) virus can cause HLH and multi-system inflammatory syndrome in children (MIS-C).