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Neutrophils are an essential arm of the innate immune response. In patients with sepsis, reprogramming of neutrophil occurs, manifest by impaired recruitment of neutrophils to sites of infection, abnormal accumulation of neutrophils to remote sites, and dysregulation of neutrophil effector responses. This review examines the mechanisms underlying dysregulated neutrophil trafficking and function during sepsis.Mechanisms governing neutrophil function in sepsis are complex. Bacterial products, cytokines/chemokines, leukotrienes, and immunomodulatory hormones can modulate neutrophil migratory responses during sepsis via induction of cytoskeletal changes, disruption of polymorphonuclear leukocyte (PMN)–endothelial cell interactions, and alterations in G-protein-coupled receptor expression or signaling. Impaired chemotactic responses and alterations in neutrophil function can occur as a result of dysregulated PMN G-protein-coupled receptor and Toll-like receptor expression and/or signaling. As sepsis evolves, neutrophil gene expression is altered, leading to suppression of proinflammatory and immunomodulatory genes, as well as decreased production of reactive oxygen species. Neutrophil extracellular traps are produced to contain and kill invading pathogens, but can paradoxically promote further tissue damage.Neutrophil migration is a coordinated process that is altered at multiple stages during sepsis. In combination with impaired neutrophil function, these alterations culminate in defective innate immunity in septic patients. Defining the mechanisms involved and strategies to interrupt these deleterious responses requires further investigation.