Neutrophil recruitment and extravasation at sites of inflammation together with the barrier functions provides by the endothelial cells play a vital role for host defense. Inactivation of uronyl 2‐O‐sulfotransferase (Hs2st) in endothelial cells has been shown to result in enhanced neutrophil recruitment in acute sterile inflammation models. Surprisingly, under real infection situation elicited by Group B Streptococcus (GBS), the leading cause for the neonate pneumonia, sepsis and meningitis, the host survival is not beneficial from the enhanced recruitment of neutrophils in the Hs2st deficient animals. In contrast, they showed increased mortality and uncontrolled bacteria organ disseminations after GBS challenge. Moreover, neutrophils from the Hs2st deficient mice were less capable to eliminate bacteria due to reduced extracellular traps formation which is critical for neutrophil bactericidal activity. In addition, increased adhesion junction disruption and apoptosis on the endothelial cells from Hs2st deficient mice was also observed. Deficiency on both neutrophils and endothelial cells contributes to the susceptibility of Hs2st deficient animals upon GBS challenge.