Background: Prematurity osteopenia is known by bone mineral content reduction, which occurs especially due to decreased mineral stores in premature infants that may be excessive by increased mineral demands in the neonatal period. Thus, the aim of this study was to detect the significance of osteocalcin as an early biomarker for preterm neonates receiving total parenteral nutrition (T.P.N) with osteopenia. Material and Methods: A Cohort study on preterm neonates receiving TPN carried out in Neonatal Intensive Care Unit of Pediatric Department, Faculty of Medicine of Zagazig University Hospitals in the period from April 2016 to September 2018. This study included 30 preterm neonates receiving (TPN) of both sexes with birth weight ≤1500gm. Comprehensive serum osteocalcin, alkaline phosphatase (ALP), calcium and phosphorus were assessed before and after TPN. Results: we found that serum levels of calcium and phosphorous showed a significant decrease after given TPN (P=0.045, P