The debate as to whether to administer ceftriaxone to neonates is likely to continue. Ceftriaxone has numerous advantages for critically ill pediatric patients. However, it is also known to contribute substantially to the development of biliary pseudolithiasis. Although pediatric patients rarely develop gallbladder disorders, this complication may lead to adverse events in high-risk patients with predisposing factors, particularly in neonates and infants treated with ceftriaxone. In this paper we present an interesting case report of a 28-day-old neonate with spontaneous severe epidural hematoma who developed biliary pseudolithiasis related to the use of ceftriaxone. We also discuss the efficacy of ceftriaxone in neonates and infants. Neonatologists and pediatric intensivists should be aware of the higher risk of co-existence of hyperbilirubinemia and gallbladder disorders while using ceftriaxone in pediatric settings.