Background: Cystic Fibrosis (CF) is a chronic disease associated with low sodium status. The patients are usually treated with oral sodium chloride to control the side effects of low sodium status. Therefore, the fractional excretion of sodium (FENa) was assessed in patients with cystic fibrosis (CF) treated with oral sodium chloride (NaCl). Methods: This was a prospective cross-sectional study that was conducted on forty children with cystic fibrosis who were under treatment with oral NaCl and were referred to Imam Hossein Hospital-Isfahan-Iran between 2017 to 2019. The patients were under treated with 2-4 mEq/kg per day oral NaCl and urinary and plasma sodium and creatinine, as well as FENa, were assessed after three months of taking NaCl. Also the patients were compared in terms of efficacy of treatment based on sodium level (between 135 and 145 mmol/L) and acceptable FENa level (between 0.5% and 1.5%). The sensitivity and specificity of FeNa and plasma sodium were assessed with ROC curve test. Results: Plasma sodium was normal in 65% of treated patients, and FENa was also normal range in 47.5% of treated patients. The treatment also was desirable for 35% of the patients. The sensitivity and specificity of FeNa were 42.9% and 57.7%, respectively, and the sensitivity and specificity of plasma sodium were 85.7% and 26.9%, respectively. Conclusion: Using of plasma sodium had higher sensitivity than FeNa and FeNa had higher specificity than plasma sodium to follow up of patients with CF.