Pulmonary resection triggers complex immune responses that can lead to postoperative lung injury (PLI). While our previous work implicated eosinophils in postoperative mortality, the roles of interleukin-5 (IL-5) and its receptor IL-5Rα—therapeutic targets in eosinophilic disorders—remain unclear in this setting. In a murine model of PLI, we unexpectedly found that neutralization of IL-5 worsened survival. Further analysis revealed that a subset of neutrophils expressing IL-5Rα exhibited cytotoxic features and contributed to tissue damage. We identified granulocyte colonystimulating factor (G-CSF) as a key upstream driver of IL-5Rα⁺ neutrophil activation, whose cytotoxicity was suppressed in the presence of IL-5. These findings uncover a previously unrecognized IL-5–G-CSF axis that regulates postoperative inflammation and highlight new therapeutic opportunities to mitigate lung injury following surgery.