Objective: To investigate the value of serum mitochondrial ATP synthase C subunit level in the evaluation of cardiac functional status and prognosis in patients with sepsis. Methods: A total of 165 sepsis patients admitted to the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Wenzhou Medical University from January 1, 2017 to December 31, 2018 were included, there were 103 males (62.4%) and 62 females (37.6%) with an age of (63±14) years. Human ATP synthase lipid binding protein (ATP5G1) ELISA kit was used to detect the level of serum ATP synthase C subunit within 24 h after admission to EICU, and compared with that in 45 healthy subjects. Clinical data of patients were collected and divided into groups according to different left ventricular ejection fraction (LVEF) and clinical outcomes. The differences in clinical indicators among each group were compared to evaluate the value of serum ATP synthase C subunit level in the evaluation of cardiac functional state and prognosis of patients with sepsis, and the independent risk factors for cardiac functional state and prognosis of patients with sepsis were analyzed. Results: Compared with the control group, the level of serum ATP synthase C subunit in the sepsis group was higher ((116±62) μg/L vs (77±34) μg/L, P<0.001). Compared with normal cardiac function group, the level of serum ATP synthase C subunit in septic cardiac dysfunction group was higher (P<0.001). Compared with the survival group, the level of serum ATP synthase C subunit in the death group was higher (P<0.05). The receiver operating curve (ROC) was drawn to analyze the value of ATP synthase C subunit, creatine kinase isoenzyme (CK-MB), B-type natriuretic peptide (BNP), troponin I (cTnI), left atrial end diastolic diameter, left ventricular end systolic diameter, left ventricular end diastolic volume, left ventricular end systolic volume in evaluating the cardiac function in patients with sepsis, and the area under the curve (AUC) was 0.928, 0.661, 0.837, 0.814, 0.703, 0.831, 0.794 and 0.765, respectively. The cut-off value, sensitivity and specificity of ATP synthase C subunit in it was 139.44 ng/L, 100% and 75.2%, respectively. ROC was drawn to analyze the prognostic value of age, urea nitrogen (BUN), ATP synthase C subunit, APACHEⅡ score and SAPSⅡ score in patients with sepsis, and the AUC was 0.719, 0.772, 0.656, 0.868 and 0.884, respectively. The cut-off value, sensitivity and specificity of ATP synthase C subunit in it was 131.24 ng/L, 61.9% and 68.7%, respectively. Logistic regression analysis showed that age, BUN, ATP synthase C subunit, cardiac dysfunction, APACHEⅡ score and SAPS Ⅱ score were independent risk factors for the prognosis of patients with sepsis. Conclusion: The level of serum ATP synthase C subunit is closely related to cardiac dysfunction in patients with sepsis, and can effectively predict the prognosis of patients with sepsis.