To study the correlation between serum creatine kinase isoenzyme (CK-MB) and cardiac troponin (cTnI) levels of neonates with hypoxic ischemic encephalopathy (HIE) and their neonatal behavioral neurological assessment (NABA) score. Methods: The clinical data of 60 neonates with HIE (in observation group) were collected between July 2018 and July 2020. According to the severity of HIE, these neonates were divided into 3 groups, which included 20 neonates with mild HIE in group A, 26 neonates with moderate HIE in group B, and 14 neonates with severe HIE in group C. Meanwhile, 60 normal neonates were selected in control group during the same period. The levels of serum CK-MB and cTnI of the neonates in these groups were detected, and the correlation between which and the NABA score of the neonates was analyzed. Receiver operator characteristic (ROC) curve was used to analyze the efficacy of the levels of serum CK-MB and cTnI of the neonates for diagnosing their HIE. Results: The levels of serum CK-MB (112.06±25.47 U/L) and cTnI (2.45±0.36 ng/L) of the neonates in the observation group were significantly higher than those (54.17±16.38 U/L and 0.10±0.04 ng/L) of the neonates in the control group, and which of the neonates in group A, group B, and group C had increased gradually. The NABA score (34.41±5.10 points) of the neonates in the observation group was significantly lower than that (39.89±7.23 points) of the neonates in the control group, and which of the neonates in group A, group B, and group C had decreased gradually (all P＜0.05). ROC curve analysis showed that the area under the curve, the sensitivity, and the specificity of the combined of the serum CK-MB and cTnI levels, and the NABA score of the neonates for diagnosing their HIE were 0.904 (0.812-0.997), 96.3%, and 87.5%, respectively, and which were significantly higher than those of the serum CK-MB and cTnI levels or the NABA score alone (P＜0.05). Spearman correlation analysis showed that the serum CK-MB and cTnI levels of the neonates were negative correlated with their NABA score (P＜0.05). Conclusion: The expressions of the serum CK-MB and cTnI of the neonates with HIE are high, and the NABA score of the neonates with HIE is low, which can be used to evaluate the severity of HIE and for predicting the occurrence of HIE. Besides, the serum CK-MB and cTnI levels of the neonates with HIE are negatively correlated with their NABA score.