Background Acute myocardial depression caused by sepsis is an important cause of early death in sepsis patients.This study aimed to evaluate the effects of levosimendan on septic myocardial depression compared with the control treatment.Methods A single-center study was conducted from Jan 15th 2019 to Jan 20th 2020.A total of 112 patients with septic myocardial depression were included and divided into levosimendan (LEV) group (n=49) and the control group (n=63) based on the administration of levosimendan.Clinical data including heart function,mechanical ventilation time,the length of intensive care unit (ICU) stay,the incidence of acute pulmonary edema and 28-day of survival rates were recorded.Results Compared with the control group,the improvement of left ventricular ejection fraction (LVEF) was greater in LEV group after one week treatment (52.41±4.62 vs.47.32±4.31,P=0.003).The level of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) decreased more significantly (1882.92± 190.61 pg/mL vs.3374.62±453.13 pg/mL,P=0.004).The mechanical ventilation time (112.43±9.11 h vs.135.34±12.54 h,P=0.013) and the length of ICU stay were also shorter (10.53±3.32 d vs.16.82±5.24 d,P=0.027) than that in the control group,and the incidence of acute pulmonary edema was lower (9.91％ vs.17.22％,P=0.041).However,Kaplan-Meier analysis indicated there was no significant difference in both group for 28-day survival rates.Conclusions Levosimendan can improve cardiac function and shorten the duration of mechanical ventilation and ICU hospitalization for septic shock patients with myocardial depression.