Carbon monoxide (CO) poisoning is the major contributor to death in fire victims. The heart is most severely affected, especially in patients with moderate to severe CO poisoning. This study aimed to assess the role of human fatty acid binding protein (H-FABP) as an easy and accurate diagnostic marker in the early detection of carbon monoxide-induced cardiotoxicity, comparing it with traditional markers such as cTn-I, CK-MB, and ECG. This study was carried out on CO-intoxicated cases presented to Benha University Hospitals for seven months. One hundred patients were selected. Suspected cardiac complications are monitored in each case by both clinical examination of the heart and vital signs and investigations that include electrocardiography (ECG) and cardiac damage biomarkers, including cardiac troponin I (cTn-I), creatine-kinase myocardium band (CK-MB), and H-FABP. ECG findings showed hypoxic changes in 14 patients (14%), where sinus tachycardia was the most common finding (75%). Measured markers of cardiac injury (cTn-I, CK-MB, and H-FABP) were elevated above normal serum levels, raising suspicion for CO-induced myocardial injury. Serial follow-up of troponin-I and CK-MB levels at 6 hours and 24 hours illustrated a non-statistically significant difference compared to a 0-hour level. Contrary to this, there was a statistically significant decrease in H-FABP level after 6 hours compared to the level at admission. Conclusion: H-FABP is more sensitive than traditional cardiac markers; it can be used to detect early cardiac injury in individuals who exhibit serious CO exposure.