Outcomes for invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO) to treat acute respiratory failure in patients with mild cystic fibrosis (CF) lung disease are not known. We present a case of the successful use of ECMO to treat acute respiratory failure secondary to staphylococcal sepsis in an adolescent CF patient with previously normal lung function. Her post-ECMO course was notable for severe airflow obstruction, hypoxemia, deconditioning, and growth failure. She had significantly improved at six months follow-up, though she continued to have moderate airflow obstruction on pulmonary function testing. This case illustrates that ECMO and prolonged intubation can prolong life in CF patients with mild lung disease who present with potentially reversible acute respiratory failure, though they are associated with significant morbidity.