Objective To investigate the predictive value of continuous non-invasive arterial pressure monitor (CNAP)combined with passive leg raising (PLR) test for volume responsiveness assessment in patients with septic shock. Methods Prospective and observational study was performed in the patients with septic shock admitted to the Fourth Department of Intensive Care Unit (ICU) of Fujian Provincial Hospital from July 2019 to July 2020. Subclavian venous catheter was indwelled in each patient, then the hemodynamic parameters including heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP),cardiac output (CO) and pulse pressure variability (PPV) were measured non-invasively by CNAP before and after PLR and volume expansion (VE) test. The changes of CO during PLR test (ΔCO_PLR) and VE test (ΔCO_VE) were calculated respectively. Patients were classified as responder group or non-responder group according to the ΔCO_VE increased ≥15% or not after VE test. Moreover,Pearson's test was used for the correlation analysis. The roles of ΔCO_PLR and PPV before VE test in predicting volume responsiveness were evaluated by receiver operating characteristic (ROC) curve. Results A total of 40 VE tests in these 36 patients were evaluated and resulting in 18 responder group and 22 non-responder group. There was no significant difference between two groups in the hemodynamics parameters before PLR and VE test (P>0.05). Both in responder group and non-responder group, there was no significant change in HR and MAP after PLR and VE test (P>0.05). After PLR, CVP did not change significantly in the two groups(P>0.05). CVP after VE test increased significantly in the two groups (P<0.05), but there was no significant difference between the two groups (P>0.05). CO was obviously increased after PLR and VE test in the two groups (P<0.05). In responder group, CO after PLR and VE test were significantly higher than those in non-responder group [(6.01±1.28) L/min vs. (5.16±1.22) L/min,(6.31±1.33) L/min vs. (5.15±1.39) L/min, P<0.05]. Besides, the ΔCO_PLR and ΔCO_VE in responder group were significantly higher than those in non-responder group (21.21%±8.54% vs. 10.76%±4.94%, 26.32%±8.64% vs. 9.44%±3.45%, P<0.05).Correlation analysis showed that the ΔCO_PLR was positively related to ΔCO_VE (r=0.820, P<0.05), while the PPV before VE test was unrelated to ΔCO_VE (r=0.194, P>0.05). Furthermore, the area under the ROC curve (AUC) of ΔCO_PLR and PPV predicting volume responsiveness were 0.855 (95%CI 0.707-0.946, P<0.05) and 0.525 (95%CI 0.362-0.685, P>0.05) respectively. The sensitivity and specificity of ΔCO_PLR ≥13.95% to predict volume responsiveness in patients with septic shock were 83.3% and 81.8%, respectively. Conclusion ΔCO_PLR measured by CNAP can predict the volume responsiveness in patients with septic shock and it is reliable to guide further fluid resuscitation.