SummaryPrevious studies demonstrated that the CXCL12 peptide analogue CTCE-0214 (CTCE) has beneficial effects in experimental sepsis induced by caecal ligation and puncture (CLP). We examined the hypothesis that CTCE recruits neutrophils (polymorphonuclear leucocytes; PMN) to the site of infection, enhances PMN function and improves survival of mice in CLPinduced sepsis with antibiotic treatment. Mice with sepsis (n = 15) were administered imipenem (25 mg/kg) and CTCE (10 mg/kg) subcutaneously versus vehicle control at designated intervals post-CLP. CTCE treatment increased PMN recruitment in CLP-induced sepsis, as evidenced by increased PMN in blood, by 2Á4 AE 0Á6 fold at 18 hr, 2Á9 AE 0Á6 fold at 24 hr, and in peritoneal fluid by 2Á0 AE 0Á2 fold at 24 hr versus vehicle control. CTCE treatment reduced bacterial invasion in blood [colonyforming units (CFU) decreased 77 AE 11%], peritoneal fluid (CFU decreased 78 AE 9%) and lung (CFU decreased 79 AE 8% versus CLP vehicle). The improved PMN recruitment and bacterial clearance correlated with reduced mortality with CTCE treatment (20% versus 67% vehicle controls). In vitro studies support the notion that CTCE augments PMN function by enhancing phagocytic activity (1Á25 AE 0Á02 fold), increasing intracellular production of reactive oxygen species (32 AE 4%) and improving bacterial killing (CFU decreased 27 AE 3%). These composite findings support the hypothesis that specific CXCL12 analogues with ancillary antibiotic treatment are beneficial in experimental sepsis, in part, by augmenting PMN recruitment and function.