Sepsis has been a serious public health concern for a long time and is characterized by disrupted development of specific diagnostic criteria and novel therapies for sepsis is critically dependent on an understanding of the basic mechanisms immune homeostasis accompanied by infection and multiple organ dysfunction as determined assessed by the Sequential Organ Failure. Adult (4 to 6 months) male C57BL/6 mice, animal set in three groups, control group, Cecal Ligation and Puncture (CLP) group, CLP+ Local sympathetic denervation group 8 mice in each group. CLP model for created sepsis and local sympathetic denervation procedure for alleviated the effects of sepsis. Assessment of cardiac function by Millar Instruments, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA) and RNA extraction and sequencing. Our findings showed that the myocardial injury score and TNF-α level in both tissue and serum were significantly increased in the CLP group. CLP with local sympathetic denervation group mice had lower scores of myocardial injuries. Sepsis augments MCP-1 and KC level in myocardium. After 48 hours after CLP, the myocardial injury score. CLP with local sympathetic denervation alleviates sepsis-induced myocardial injury by inhibiting the NF-κB signaling pathway. Moreover, compared with the Ctrl group, the CLP with local sympathetic denervation group obtained fewer ncRNAs and mRNAs. Inconclusions, the NF-κB signaling pathway is associated with sepsis-induced myocardial injury, and local sympathetic denervation can relieve sepsis-induced myocardial injury by regulating the ncRNAs and mRNAs.