To identify the effect of normal breathlessness sensation elicited during intense intermittent exercise at exhaustion on limitation of exercise maintenance (Ex), the contribution of the flow-resistive unloading effect of normoxic helium-oxygen breathing on the breathlessness sensation to the change in the Ex was examined. Seven men repeatedly performed 12-s exercise at 160% maximal aerobic power output followed by passive recovery for 18-s under normal (CON) and unloaded (UL) breathing conditions until exhaustion. In UL, Ex was enhanced [mean (SD) 127.2 (11.8)% CON] concomitantly with reduction in averaged peak inhaled mouth pressure (PPmi) of recorded breathing cycles that reflected approximate true inspiratory muscle force output. At the iso-time point of CON exhaustion, the reduction in PPmi to [75.7(10.2)% CON] in UL was concomitant with the reductions in the rating of perceived breathlessness (RPB) [87.5 (13.1)% CON] and in the slope of time course for RPB (RPB/2-min period) [82.1 (17.2)% CON]. It was also concomitant with increases in ventilation and total oxygen consumption. However, the augmented oxygen consumption did not result in lowering of subjects' metabolic stress that was indicated by accumulations of blood lactate and plasma ammonia and uric acid. Nevertheless, the reductions in the RPB and RPB/2-min period, which reflected the breathlessness intensity, were correlated to the CON Ex enhancement in UL (RPB r=-0.57, RPB/2-min period r=-0.83; P<0.05). These findings implied that the normal noxious breathlessness sensation elicited during intense intermittent exercise at exhaustion might contribute to the limitation of subjects' exercise maintenance.