We report a case of Dubin-Johnson Syndrome in a neonate presenting with severe direct hyperbilirubinemia, which failed to respond to phenobarbital treatment. Ursodeoxycholic Acid added to therapy was well tolerated, and resulted in declining bilirubin concentration. We suggest ursodeoxycholic acid in treatment for Dubin-Johnson Syndrome with severe direct hyperbilirubinemia presenting in the neonatal age.