Abstract: Objective To discuss clinical efficacy of creatine phosphate sodium in treating neonatal hypoxic ischemic encephalopathy(HIE) with myocardial damage and probable mechanism. Method Ninety-two HIE patients with myocardial damage in our hospital were randomly divided into control group (46 cases) and treated group(46 cases) with reference to digital table method.All patients were treated with supportive treatment including low flow oxygen therapy and so on.Patients of control group were given single sialic acid four hexose ganglion glucoside ester sodium intravenous drip(20 mg/time,qd).Patients of treatment group were given creatine phosphate sodium based on treatment of control group(0.5-1.0 g/time,qd).Courses for two groups were 2 weeks.Serum creatine kinase(CK),cardiac troponinI(cTnI) and creatine kinase-MB(CK-MB) in two groups were compared.Expression of serum nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2)in two groups were detected by immunoblotting.Serum levels of reactive oxygen species(ROS),nitric oxide(NO),nuclear factor-κB(NF-κB),tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 were detected in two groups. Results Serum levels of CK,cTnI and CK-MB after treatment were obviously lower in treatment group than those of control group(P＜0.01).LVEF and E/A after treatment in treatment group were evidently higher than those of control one(P＜0.01).After treatment,serum NOX2,ROS,NO,NF-κB,TNF-α and IL-6 in treatment group were obviously lower thanthose of control one with statistically significant difference(P＜0.01). Conclusion Creatine phosphate sodium could reduce the myocardial injury markers effectively,improve heart function in treating HIE.One of the probable mechanisms may be related to restraining NOX2/ROS oxidative stress pathways and mitigating downstream inflammatory lesions.