Bacterial infection is the most common cause ofsepsis. In this study, Phascolosoma esculenta oligosaccharides(PEOs) were prepared to evaluate their resistanceagainst E. coli-induced sepsis. HPLC–MS and FT-IRindicated that PEOs were composed of D-glucosyl, Dgalactosyl,with small amount of D-mannosyl, D-arabinosyland residues with a- and b-type linkage. Different dosageadministrations of PEOs for 30 days significantly improvedICR mice survival rate and bacterial clearance ability(P\0.01) after as E. coli injection. Moreover, PEOs significantlyreduced the secretion of IL-1b and TNF-a andenhanced that of IL-10 in sepsis mice, enhanced theantioxidant enzyme activities and total antioxidant capacity,decreased MDA level in the serum, and upregulatedmRNA expression of Nrf2 (P\0.01). All these resultsindicate that PEOs could improve the resistance of ICRmice against E. coli-induced sepsis that attributed to antiinflammatoryand anti-oxidative stress.