Objective To explore the role of systemic immune-inflammation index (SII) combined with monocyte to high density lipoprotein-cholesterol ratio (MHR) in predicting myocardial injury in patients with acute carbon monoxide poisoning (ACOP). Methods A total of 113 ACOP patients who were admitted to Department of Emergency of Harrison International Peace Hospital Affiliated to Hebei Medical University, Department of Emergency of Affiliated Hospital of Hebei University, and Department of Emergency of North China University of Science and Technology Affiliated Hospital from Jan. 2020 to Mar. 2022 were enrolled and divided into myocardial injury group (n＝30) and non-myocardial injury group (n＝83). The levels of SII, MHR, C reactive protein (CRP), cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) were detected at admission and 12 h after admission. The independent risk factors of myocardial injury in ACOP patients were analyzed by logistic regression. The early predictive values of SII, MHR and their combination for myocardial injury in ACOP patients were analyzed by receiver operating characteristic curves. Results The levels of SII, MHR and CRP of patients in the myocardial injury group were higher than those in the non-myocardial injury group at admission, and the levels of SII, MHR, CRP, cTnI and CK-MB of patients in the myocardial injury group were higher than those in the non-myocardial injury group at 12 h after admission (all P＜0.001). The elevated levels of SII, MHR and CRP were risk factors for myocardial injury in ACOP patients (odds ratio＝7.248, 5.733, 2.496, all P＜0.05). The AUC value, sensitivity and specificity of SII combined with MHR were higher in predicting myocardial injury in ACOP patients at admission (0.876, 0.867 and 0.766, respectively). Conclusion The combination of SII and MHR has early predictive value for myocardial injury in ACOP patients.