Objectives: To evaluate plasma protein Z (PZ) levels in healthy and high-risk newborn infants. Background: Protein Z (PZ) is a vitamin K-dependent plasma protein , As is the case with other coagulation proteins and inhibitors, protein Z is consumed during disseminated intravascular coagulation (DIC), Functionally protein Z has been shown to be a direct requirement for the binding of thrombin to endothelial phospholipids , Protein Z also serves as a cofactor for the inhibition of coagulation factor Xa by a plasma serein called protein Z-dependent protease inhibitor (ZPI), The inhibitory function is exerted by the Protein Z-dependent protease inhibitor (ZPI), which circulates in the human plasma in a complex with PZ , The physiological function of protein Z is still rather ill-defined and may play role in high risk newborn. Methods: This study was conducted on 85 newborns divided in 4 groups ,(group I newborns affected by respiratory distress syndrome (RDS) , group II newborns from mothers with pre-eclampsia, group III newborns small for gestational age (SGA) and group IV healthy term and preterm newborns normal for gestational age. Newborns with sepsis, congenital malformation or hemorrhagic disorders were excluded, Plasma PZ levels was measured. Results: In the neonates of the study groups, protein z level was significant lower in patient group than control group, in group I (0.79 ±0.32), group II (0.70± 0.30), group III (0.78 ±0.32) and group IV (1.44 ±0.43) (p value<0.001). Conclusion: PZ deficiency occurs in newborns affected by severe RDS, in newborns from preeclampsic mothers and in SGA newborns, probably owing to activated coagulation in the first two conditions and to reduced PZ synthesis in the last one.