Abstract Background Early hemodynamic assessment of critically ill newborns requires mostly invasive measurements in neonatal intensive care unit. Base deficit and serum lactate concentrations may be important prognostic indicators in preterm infants. Aim and Objectives to investigate the relationship between serum lactate levels and adverse outcome in preterm infants who were admitted to NICU of Ain Shams University Hospital. Subjects and Methods This study is prospective cohort study, that included 90 preterm patients that were admitted to neonatal intensive care unit during a period of 6 months, all the neonates had the level of serum lactate been evaluated by ELISA (at 6, 12, 18 and 24 hours of birth) and correlated with the incidence of intracranial hemorrhage as diagnosed by cranial ultrasonography. Result: The initial serum lactate level was compared with the follow up readings at 12, 18 and 24 hours and showed statistically significant reduction of serum lactate in follow up recordings (p-value <0.05), Serum lactate was statistically significant predictors of death with increase serum lactate at 12hrs., at 18hrs. and at 24hrs, with p-value (p < 0.05). Serum lactate had no statistically significant association with intracranial hemorrhage as detected by transcranial ultrasonography. Conclusion Serial lactate measurements greater than 5.6 mmol/l predict adverse outcome and may aid the clinician in bedside decision making.