This study aimed to explore the role and mechanism of Mettl1 in septic cardiomyopathy, and analyze its effect on the mechanism of cuproptosis. The impact of 20 SPF grade C57BL/6N mice were randomly divided into model group (n=10) and control group (n=10). The model group was treated with intraperitoneal injection of LPS (10 mg/kg) to construct septic cardiomyopathy. Cardiac function was assessed by echocardiography, and myocardial pathological changes, inflammatory factors and the expression of Mettl1, Wdr4, Fdx1 and Akt genes were analyzed by HE staining, flow cytometry, enzyme linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB) and other techniques. Compared with the normal group, the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS) and left ventricular end systolic diameter (LVESD) of the model group mice are significantly reduced (P < 0.01), and myocardial tissue damage is significant. The mRNA expressions of Mettl1, Fdx1, Wdr4 and Akt are also significantly increased. After silencing Mettl1, the levels of inflammatory factors TNF-α, IL-6 and oxidative stress indicators MDA and ROS in septic cardiomyocytes are significantly decreased (P < 0.01), and the gene expression levels of Wdr4, Fdx1 and Akt are significantly decreased (P < 0.01). Mettl1 plays an important role in cuproptosis signaling pathway in septic cardiomyopathy. Silencing Mettl1 can reduce the levels of inflammation and oxidative stress in cardiomyocytes and regulate the expression levels of Wdr4, Fdx1 and Akt genes related to cuproptosis signaling, suggesting its value as a potential therapeutic target.