Background The effect of CFTR modulators on exercise capacity in people with CF (pwCF) is controversial. In addition, the effect of elexacaftor/tezacaftor/ivacaftor (ETI) on improving exercise capacity after an exercise intervention is not known. We aimed to evaluate the effects of an exercise intervention in adult pwCF in the presence or absence of ETI treatment. Methods 56 adult pwCF participated in an exercise intervention during a 4-week rehabilitation course. The exercise program consisted of 5 sessions per week of 45 minutes each, including 3 endurance sessions on a cycle ergometer. Peak oxygen uptake (VO2peak) and peak workload (Wpeak) were used as primary outcomes to assess changes in exercise capacity. Results The training intervention led to a significant increase in VO2peak and Wpeak in all pwCF with or without ETI. The degree of improvement did not differ between the groups treated with and without ETI. PwCF with lower fitness (VO2 ≤ 81%pred) benefited more than pwCF with higher fitness (VO2peak ≥82%pred). The degree of improvement in VO2peak and Wpeak in the fitness groups with and without ETI was comparable and did not differ significantly from each other. Conclusion The use of ETI has little or no effect on the degree of improvement in VO2peak and Wpeak. This suggests that other factors, such as level of exercise capacity and physical inactivity, may determine the degree of improvement in exercise capacity in adult pwCF. In general, adult pwCF with and without ETI benefit from exercise interventions and can improve their exercise capacity.