objective To explore the differences in the efficacy of PiCCO monitoring and ultrasound in guiding early fluid resuscitation in patients with sepsis. Methods In December 2017 - December 2018, with a random number table cangzhou people"s hospital of intensive medicine confirmed 98 cases of sepsis patients were randomly divided into control group (PiCCO monitor based on guidance of early fluid resuscitation) and experimental group (ultrasound guidance on the basis of early fluid resuscitation), compared two groups of patients with general clinical data (HR, MAP, urine output, SvO2) and rating scale (APACHE Ⅱ and SOFA), biochemical index content (IL - 10, ET - 1, NT - proBNP, LAC) within the group, the differences between groups. Result After treatment than before treatment, two groups of patients" HR, APACHE Ⅱ and SOFA score IL - 10, ET - 1, LAC content were decreased, and the MAP, urine output, SvO2, NT - proBNP content were increased, interclass difference had statistical significance (P< 0.01). After treatment, HR of the experimental group (104.51±10.34 times /min) was lower than that of the control group (112.40±10.16 times /min), MAP (69.84±5.60mm Hg), urine volume (1393.51± 180.95ml) and SvO2 (75.63±6.27%) of the experimental group were higher than those of the control group (63.12±4.23mm Hg), (969.74± 169.89ml) and (69.22±5.38%). Group APACHE Ⅱ (82.40 ± 8.29), the SOFA (22.60±2.63) score were lower than the control group (97.23 ±5.13), (27.54±1.32), The content of IL-10 (35.27±3.63ng/L), ET-1 (152.63±12.94pg/L), LAC (3.15±0.61mmol/L) in the experimental group was lower than that in the control group (43.85±3.11ng/L), (212.02±15.73pg/L), and (4.86±1.04mmol/L). The content of Nt-probNP in the experimental group (4561.12±384.50ng/mL) was higher than that in the control group (4106.07±403.99ng/mL). The differences between groups were statistically significant (P<0.01). Conclusions Ultrasound examination is used to guide early fluid resusitation in patients with sepsis, and has a better effect than PiCCO monitoring, which can significantly reduce inflammation in the body, enhance cardiac function and blood oxygen status.