Background: Adults with cystic fibrosis (CF) suffer from chronic inflammation, infection, and airway obstruction, and often have enhanced sputum production. Although CF transmembrane conductance regulator modulator therapies such as elexacaftor-tezacaftor-ivacaftor (ETI) confer lung function gains in patients with CF, their impact on inflammation and infection is not fully understood. CF sputum contains metabolites and proteins that reflect inflammation. We hypothesized the impact of ETI therapy on CF airway inflammation would be mirrored by changes in the sputum metabolome.