Septic patients with worst clinical prognosis have increased circulating immature granulocytes (IG), displaying limited phagocytosis and reactive oxygen species (ROS) production. Here, we developed an ex vivo model of incubation of human granulocytes, from septic patients or healthy donors, with Escherichia coli. We showed that the ROS production in Sepsis-IG is lower due to decreased activation and protein expression of the NADPH oxidase complex. We also demonstrated that the low level of ROS production and lower phagocytosis of IG in sepsis induce the bacterial SOS response, leading to the expression of the SOS-regulated quinolone resistance gene qnrB2. Without antimicrobial pressure, the sepsis immune response alone may promote antibiotic resistance expression. Display omitted •Immature granulocytes in sepsis have decreased phagocytosis and ROS production•SOS response is induced in granulocyte-phagocyted bacteria and is ROS dependent•The level of bacterial SOS induction depends on granulocyte maturation and priming•Phagocyted bacteria induce SOS-dependent quinolone resistance qnrB2 expression Immunology; Microbiology; Bacteriology