Objective To explore the effect of Shuxuening on early myocardial injury markers and oxidative stress in severe sepsis patients with myocardial injury. Methods A total of 102 severe sepsis patients with myocardial injury, who received therapy in our hospital from Mar. 2013 to Jun. 2016, were randomly divided into two groups: control group (51 cases) and therapy group (51 cases). The patients in the control group received routine treatments and the therapy group were given Shuxuening based on routine treatment. We detected the levels of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid binding protein (hFABP), cardiac troponin I (cTnI), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of patients before treatment (at admission), after treatment for 6 h and 72 h (after admission), and analyzed the change of left ventricular ejection fraction (LVEF), acute physiology, chronic health evaluation (APACHE) Ⅱ score, length of ICU stay and 28-day mortality of the patients. Results At admission, there was no difference in the levels of plasma NT-proBNP, hFABP, cTnI, MDA, SOD, GSH-Px, APACHE Ⅱ score or LVEF between the two groups (P>0.05). After treatment for 6 h, the levels of plasma NT-proBNP, hFABP, cTnI and MDA in the therapy group were significantly lower and the activities of plasma SOD and GSH-Px were significantly higher than those in the control group (P<0.05); the two groups both had significant increases in the levels of NT-proBNP, hFABP, cTnI and MDA and significant decreases in the activities of SOD and GSH-Px compared with those before treatment (P<0.05). After treatment for 72 h in the two groups, the levels of plasma hFABP and MDA were significantly lower and the levels of plasma NT-proBNP and cTnI, the activities of SOD and GSH-Px were significantly higher than those after treatment for 6 h (P<0.05). After treatment for 72 h, the levels of plasma NT-proBNP, cTnI and MDA in control group were significantly higher and the activities of plasma SOD and GSH-Px were significantly lower than those in the therapy group (P<0.05), with the difference in the hFABP levels being similar in the two groups (P>0.05). APACHE Ⅱ scores after treatment were significantly lower than that before treatment in the two groups (P<0.05), and no significant difference was found in the LVEF or the length of ICU stay after treatment between the two groups (P>0.05). The therapy group had a significantly lower 28-day mortality than the control group (P<0.05).The therapy group had a significantly lower mortality than the control group (P<0.05). Conclusion Therapeutic effect of Shuxuening on the severe sepsis patients with myocardial injury is superior to the routine treatment. Shuxuening can decrease the levels of NT-proBNP, hFABP, cTnI, and MDA and APACHE Ⅱscore, and can increase the activities of SOD and GSH-Px.