We report the fatal case of neonatal fulminant hepatic failure due to Echovirus infection mimicking an acute metabolic decompensation. After exclusion of several metabolic disorders, the diagnosis of the infectious etiology was confirmed by Polymerase Chain Reaction of Echovirus in liver and spleen tissue. Establishment of etiological diagnosis and exclusion of inherited metabolic disease helped the family counseling regarding risk for future pregnancies. Fulminant hepatic failure in the neonate is a diagnostic and therapeutic challenge that requires a multidisciplinary management. Our case illustrates the broad differential diagnosis, the common final pathway leading to severe liver injury, and the multidisciplinary approach to diagnosis and treatment.