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Purpose: In obesity, an increased work of breathing contributes to a higher O2 cost of exercise and negatively affects exercise tolerance. The purpose of the study was to determine whether, in obese adolescents, acute respiratory muscle unloading via normoxic helium-O2 breathing reduces the O2 cost of cycling and perceived exertion., Methods: Nine males [age 16.8 ± 1.6 (x ± SD) years, body mass 109.9 ± 15.0 kg] performed on a cycle ergometer, breathing room air (AIR) or a 21 % O2-79 % helium mixture (He-O2): an incremental exercise, for determination of [Formula: see text]O2 peak and gas exchange threshold (GET); 12 min constant work rate (CWR) exercises at 70 % of GET (GET) determined in AIR., Results: [Formula: see text]O2 peak was not different in the two conditions. From the 3rd to the 12th minute of exercise (both during CWR < GET and CWR > GET), [Formula: see text]O2 was lower in He-O2 vs. AIR (end-exercise values: 1.40 ± 0.14 vs. 1.57 ± 0.22 L min(-1) GET). During CWR > GET in AIR, [Formula: see text]O2 linearly increased from the 3rd to the 12th minute of exercise, whereas no substantial increase was observed in He-O2. The O2 cost of cycling was ~10 % (GET) lower in He-O2 vs. AIR. Heart rate and ratings of perceived exertion for dyspnea/respiratory discomfort and leg effort were lower in He-O2., Conclusions: In obese adolescents, acute respiratory muscle unloading via He-O2 breathing lowered the O2 cost of cycling and perceived exertion during submaximal moderate- and heavy-intensity exercise.