In sepsis, hyperactivation of neutrophils can lead to tissue injury. Later, neutrophil dysregulation with reduced levels of migration, decreased apoptosis and inadequate phagocytosis may impair the host׳s ability to clear infection. Lipoxin A 4 (LXA 4 ) is a pro-resolution lipid mediator which reduces neutrophil migration and inflammatory mediator expression. As neutrophil migration and activation are important in bacterial clearance, the role of LXA 4 in regulating neutrophil function for bacterial clearance is unclear. Using the cecal ligation and puncture (CLP) rat model of sepsis, LXA 4 given after 1h reduced blood bacterial load at 24h. LXA 4 treatment decreased neutrophil migration to the peritoneum but augmented blood neutrophil phagocytic ability and promoted apoptosis without affecting free radical production. In contrast, LXA 4 increased peritoneal neutrophil phagocytic ability without affecting apoptosis or free radical production suggesting that in vivo effects of LXA 4 were compartment specific. To investigate if LXA 4 acted directly on neutrophils, blood and peritoneal leukocytes were taken from CLP rats 1h after surgery and incubated ex vivo with and without LXA 4 . LXA 4 (1nM) increased phagocytosis in blood neutrophils without affecting apoptosis or free radical production. Ex vivo LXA 4 had no effect on peritoneal neutrophils which suggests that LXA 4 enhanced peritoneal neutrophil phagocytic ability in vivo by an indirect mechanism. The results suggest that LXA 4 reduced neutrophil migration, but increased neutrophil bacteria clearing function without excessive free radical production. This phenotype was associated with reduced blood bacteria load.