Recent studies have shown that therapy with Cystic fibrosis transmembrane conductance regulator (CFTR) modulators in Cystic Fibrosis (CF) patients with Elexacaftor-Tezacaftor-Ivacaftor (ETI) decreases exacerbations and improves lung function and quality of life. Objective: to report the clinical response in the first patient in our setting treated with ETI. Clinical Case: 14-year-old female patient with severe cystic fibrosis phenotype, heterozygous for the Phe508del mutation (Phe508del/1078delT), with moderate pulmonary involvement and pancreatic insufficiency (PI). The patient started ETI therapy after the disease entered a phase of clinical and pulmonary function deterioration. From the second visit (45 days) until the end of the follow-up (365 days), the patient experienced a significant improvement in the quality-of-life domains measured by the CFQ-R 14+ questionnaire. In the pulmonary function study at 45 and 365 days, FVC increased by 21% and 22%, FEV1 by 20% and 27%, and FEF 25-75 by 23% and 37%, respectively. Nutritional assessment parameters in the first six months of follow-up showed an increase in wBMI from 1.6 to 5.6 k. No adverse effects were observed. Conclusion: treatment with ETI in our CF patient showed a remarkable improvement in quality of life, pulmonary function, and nutritional status.