Background: Maximal cardiopulmonary exercise testing is recommended on an annual basis for children with cystic fibrosis (CF), due to clinically useful prognostic information provided by maximal oxygen uptake (V̇O 2max ). However, not all patients are able, or willing, to reach V̇O 2max , and therefore submaximal alternatives are required. This study explored the validity of the oxygen uptake efficiency slope (OUES) as a submaximal measure of V̇O 2max in children and adolescents with CF., Methods: Data were collated from 72 cardiopulmonary exercise tests (36 CF, 36 controls), with OUES determined relative to maximal and submaximal parameters of exercise intensity, time, and individual metabolic thresholds. Pearson's correlation coefficients, independent t-tests, and factorial ANOVAs were used to determine validity., Results: Significant (P < 0.05) correlations with V̇O 2max were observed for most expressions of OUES, but were consistently weaker in CF (r = 0.30-0.47) when compared to CON (r = 0.58-0.89). Mean differences for all OUES parameters between groups were not significant (P > 0.05). When split by V̇O 2max tertiles, minimal significant differences were found between, and within, groups for OUES, indicating poor discrimination of V̇O 2max ., Conclusions: The OUES is not a valid (sub) maximal measure of V̇O 2max in children and adolescents with mild-to-moderate CF. Clinicians should continue to use maximal markers (ie, V̇O 2max ) of exercise capacity., (© 2017 Wiley Periodicals, Inc.)