INTRODUCTIONNon-syndromic paucity of interlobular bile ducts (NSPIBD) is a rare cause of neonatal cholestasis, and its incidence and prevalence have not yet been precisely established.  The clinical presentation of NSPIBD closely resembles that of extra-hepatic biliary atresia, and it can be missed unless an infant with neonatal cholestasis undergoes a comprehensive workup that includes a liver biopsy. Histopathological findings typically show portal changes such as duct paucity and fibrosis, as well as lobular changes including cholestasis, giant cell transformation, extramedullary haematopoiesis and perisinusoidal fibrosis. This case report aims to outline the spectrum of clinical presentation of NSPIBD in an infant with Down syndrome, as well as the course and outcomes of this condition in infants with this genetic disorder. Treatment primarily involves supportive management of cholestasis, and the reported prognosis of NSPIBD in this patient population is variable.