Abstract: Objective To analyze the effect of acid-base disorder on myocardial enzymes in full-term neonates with hyperbilirubinemia. Methods A total of 100 full-term neonates with hyperbilirubinemia who were admitted in Department of Neonates, the Second Affiliated Hospital of Nanjing Medical University from October 2018 to June 2021 were selected as a non-etiological jaundice group. Meanwhile, another 100 neonates with ABO hemolytic jaundice, 100 neonates with asphyxia and 100 neonates with pneumonia were set as a hemolytic jaundice or other disease control groups. According to the severity of neonates in the non-etiological jaundice group and the hemolytic jaundice group, they were divided into a high-risk jaundice group (61 cases) and a middle-risk group (39 cases), as well as a hemolytic high-risk jaundice group (50 cases) and a middle-risk group (50 cases). Their levels of serum total bilirubin, myocardial enzymes spectrum, blood electrolyte, blood routine, and blood gas values were analyzed. The relationship between myocardial enzymes and acid-base balance in each group was evaluated. Results There were significant differences in cardiomyoenzyme spectrum among the groups (P<0.05). Compared with the asphyxia group, the non-etiological jaundice group showed statistical differences in myohemoglobin (Myo) and creatine kinase MB (CK-MB)(P<0.05), without statistical difference in cardiac troponin T (cTnT) (P>0.05); there were statistical differences in Myo, CK-MB and cTnT in the hemolytic jaundice group and the pneumonia group (P<0.05).There was no significant difference in CK-MB among different-degree acid-base disorder groups (P>0.05), but with significant differences in Myo and cTnT (P<0.05), which was related to disorder types. Conclusions Full-term neonatal hyperbilirubinemia has the same degree of myocardial enzyme changes as neonatal asphyxia. Myocardial enzyme changes are related to acid-base disorder, rather than jaundice degree. The analysis of blood gas triple acid-base disorder is helpful to discover the cause of neonatal hyperbilirubinemia with myocardial injury, and provides basis for clinical diagnosis and treatment.