The lack of effective antiinflammatory therapies for people with CF (PWCF) represents a significant challenge.<b>Objectives:</b> To identify altered immunometabolism in the CF neutrophil and investigate the feasibility of specific inhibition of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome as a CF antiinflammatory strategy <i>in vivo</i>.<b>Methods:</b> Key markers of increased aerobic glycolysis, known as a Warburg effect, including cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, succinate, HIF-1α (hypoxia-inducible factor-1α), lactate, and the IL-1β precursor pro-IL-1β, as well as caspase-1 activity and processing of pro-IL-1β to IL-1β by the NLRP3 inflammasome, were measured in neutrophils from blood and airway secretions from healthy control subjects (<i>n</i> = 12), PWCF (<i>n</i> = 16), and PWCF after double-lung transplantation (<i>n</i> = 6).