Background: Exercise performance is reduced in individuals with moderate to severe cystic fibrosis (CF). A ventilatory mechanical limitation, arterial hypoxemia, cardiovascular abnormalities, alteration in O2 uptake kinetics and reduced muscle strength may contribute to the reduced exercise performance in individuals with CF patients. The purpose of this research was to compare the exercise response in patients with different CF severities using non- invasive methods, and examine the effect of exercise training with and without O2 supplementation on exercise performance. Methods: Study 1: Adults (n=33) with different severities of CF and healthy controls (n=34) had their body composition, and pulmonary function assessed, and performed a peak exercise test. Study 2: Adults (n=28) with different severities of CF and healthy controls (n=19) had their muscle strength, pulmonary function, body composition and V̇O2peak assessed, and performed a submaximal exercise tests. Study 3: Adults with different severities of CF who were randomly assigned to a placebo (n=6) or O2 supplemental (O2Suppl) (n=5) group undertook interval training on a cycle ergometer 2 days/week for 8 weeks (single blind). Body composition, pulmonary function, V̇O2peak, muscle strength, time to complete a 6 minute walk and performance during a constant work load submaximal tests were assessed before and after the training study. Results: Peak exercise capacity and muscle strength were reduced and O2 uptake kinetics was slower in CF patients than healthy controls. The provision of supplemental O2 during training improved O2 uptake kinetics and resulted in a decrease in ventilation, respiratory rate and blood lactate levels during exercise. Conclusion: Depending on disease severity, the reduction in exercise capacity in CF patients is related to a reduced lean body mass, reduced gas exchange, ventilatory limitation, and an altered cardiovascular response. The provision of supplemental O2 during exercise training may improve endurance capacity in patients with CF.