Background: Creatine kinase MB (CK-MB), which exists mainly in the cytoplasm of myocardial cells, is currently accepted as an indicator and has high sensitivity and specificity for the diagnosis of myocardial injury. Objective: This study was aimed to estimate serum creatine kinase MB (CK-MB) levels after asphyxia-induced myocardial injury in neonates. Patients and methods: 40 neonates were included in this study and divided into 20 cases with the diagnosis of perinatal hypoxia ischemia and 20 controls admitted to Neonatology Unit of Pediatric Department at Zagazig University.  Serum CK-MB levels were estimated in all studied neonates.   Results: In the present study serum CK-MB levels in cases were significantly higher than controls. A significant area under curve with cutoff >14.5 (units /L) with sensitivity 99%and specificity 97.5% for CK-MB.  Encephalopathy cases were significantly associated with higher HR and CKMB. Cases with organ failure were significantly associated with higher HR and CKMB. Cases with metabolic acidosis were significantly associated with higher HR and CKMB. Conclusion: It could be concluded that cases with hypoxic ischemic encephalopathy (HIE) and those with multiple organ failure had a more pronounced elevation of serum CK-MB compared with cases of hypoxia-ischemia with no organ failure. Similarly, patients with HIE had significant elevation of cardiac enzymes. Collectively, these findings indicate more myocardial systolic dysfunction and damage in neonates with HIE and organ failure.