Background: Accurate assessment of pulmonary status in young children with cystic fibrosis (CF) requires sensitive and objective monitoring techniques. Objectives: This study aimed to evaluate the feasibility of lung clearance index (LCI) calculated from multiple breath washout (MBW), home nocturnal pulse oximetry and home nocturnal cough recording in young children with CF, and determine whether these tests can distinguish CF patients from healthy controls. Methods: We performed a prospective cross-sectional study in 20 CF patients and 30 healthy children aged 0-4 years. MBW was performed in awake and unsedated children at the outpatient clinic using a commercially available device. Measurements of nocturnal oxygen saturation and nocturnal cough were done at home using a pulse oximeter and an audiometer. Results: There was a significant difference in mean LCI between healthy children and CF patients (LCI 7.1 vs. 9.3, p<0.001). Nocturnal oxygen saturation was normal in both groups and did not significantly differ between the groups. Similarly, cough showed no differences between both groups. Cough varied widely between children and between nights. Success rates for saturation and cough measurements were 90% and were similar for CF patients and healthy children. Success rate for LCI was 75% for CF Conclusions: Measurements of LCI, nocturnal oxygen saturation and cough were feasible in young children; however LCI was the only variable that showed a significant difference between children with CF and healthy children. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.