The dysregulated host response to infections can lead to sepsis, a complex disease characterized by a spectrum of clinical phenotypes. Using scRNA-seq, we analyzed the immune cell of survived and non-survived CLP-septic mice to gain insights into the immunological mechanisms by which neutrophils contribute to the hyperinflammatory phenotype. Our findings reveal that non-survived mice exhibit increased frequencies of immature CXCR4(+) PD-L1(+) neutrophils in the bloodstream, accompanied by an accumulation of trafficking-specific CXCR4(+) PD-L1(+) neutrophils into the lungs. The IFN-gamma and LPS promote the PD-L1 expression on neutrophils and an activation profile associated with inflammation and organ damage. Notably, abrogating the IFN-gamma reduced susceptibility to CLP-sepsis and diminished CXCR4(+) PD-L1(+) neutrophils frequency. This study provides insights into the immune cell activation profiles associated with the worsening of the CLP-sepsis, and the CXCR4(+) PD-L1(+) neutrophils population highlighted here represents a promising target for therapeutic modulation in clinical sepsis hyperinflammatory phenotype.