Background: Heart failure is one of the cardiovascular diseases that have high morbidity and mortality especially among children. It accounts for 2% of all pediatric inpatient admission. Cardiac Myosin Binding Protein-C (cMyBP-C) is cardiomyocyte specific sarcomeric protein that regulates sarcomeric structure and its function where it is released in circulation in response to cardiac injury. Objective: To explore the role of cMyBP-C as a biomarker in heart failure in children. Patients and Methods: This prospective cohort study was carried out during the period from October 2017 to October 2018 in Pediatric Cardiology Unit, Zagazig University Hospital. It included 26 selected patients with heart failure diagnosed clinically and by echocardiography. Results: The study revealed that the most common cause pf heart failure in our patients was VSD (30.8%) then DCM (26.9%). 57.7% of studied patients were grade III of ROSS classification while 30.8% were grade IV and 11.5% were grade II. In ECHO findings, mean EF% was 52.3% while mean FS% was 33 % with negative correlation between plasma level of cMyBP-C and EF% and FS%. There was high statistical significant difference in cMyBP-C plasma level at time of admission and after treatment (123.5 ng/ml and 78.8 ng/ml respectively). There was high statistical significant difference in level of cMyBP-C among improved cases before and after treatment. There was no statistical significant difference in level of cMyBP-C before and after treatment among cases with bad prognosis. Conclusion: cMyBP-C could be a prognostic biomarker in children with HF and may be used as a tool to help in HF diagnosis in children as a marker of disease severity.