The aim of this study was to compare the cardiac function index (CFI) and global ejection fraction (GEF) obtained by VolumeView/EV1000™, with the left ventricular ejection fraction (LVEF) by echocardiography in septic shock patients. A prospective observational study was conducted in a medical intensive care unit of a tertiary, teaching university hospital. Thirty-two, mechanical-ventilated septic shock patients were included in this study. We simultaneously measured CFI and GEF with LVEF. The correlation of CFI, GEF along with LVEF and ability of CFI and GEF to predict LVEF ≥ 40, 50 and 60% were evaluated. There were 192 pairs of CFI, GEF and LVEF. CFI was significantly correlated with GEF (r = 0.82, P < 0.0001). A significant correlation was observed between CFI and LVEF (r = 0.56, P < 0.0001) and GEF and LVEF (r = 0.71, P < 0.0001). The CFI and GEF had a good predictive ability for estimating LVEF ≥ 40, 50 and 60%, with an area under receiving operating characteristic (AUC) 0.875–0.934. The CFI ≥ 3/min predicted LVEF ≥ 40% with sensitivity 95.1% and specificity 48.3%. The GEF ≥ 15%, estimated LVEF ≥ 40% with sensitivity 92.6% and specificity 69%. There were 40 thermodilution and LVEF measurements obtained before and after norepinephrine adjustment. Blood pressure as well as the cardiac index were significantly increased, whereas there were no changes in CFI, GEF and LVEF values. Conclusions: Both CFI and GEF obtained by VolumeView/EV1000™, correlated with LVEF, so as to provide a reliable estimation of LV systolic function in septic shock patients.