To identify potential targetable mechanisms controlling neutrophil degranulation in systemic infection, we investigated alterations in neutrophil developmental state under severe inflammation. We performed tandem mass tag (TMT) proteomics on neutrophils isolated from peripheral blood of sepsis patients. We collected blood from patients with septic shock at Bristol Royal Infirmary (United Kingdom, n = 4). For each patient group, we collected matched healthy controls (HC) from the same populations. We performed longitudinal sampling at days 1 (T1), 4 (T2), 10 (T3) and 25 (T4) post admission to intensive care.