Expiratory flow limitation results in dyspnea, dynamic hyperinflation leading to low inspiratory reserve volume, and premature exercise intolerance. Unknown is whether expiratory flow limitation reduces locomotor power via fatigue in the motor activation system, exacerbating skeletal muscle fatigue, or both. The hypotheses were: 1) Imposed expiratory resistance reduces locomotor power and exercise tolerance. 2) Expiratory resistance increases activation fatigue. 3) Activation fatigue is most closely related to dynamic hyperinflation and dyspnea. To investigate, healthy volunteers performed a series of cycling exercise tests with and without an imposed expiratory flow resistance. Participants completed constant power cycling to intolerance followed with a maximal 5 s isokinetic sprint. A third trial was completed without expiratory resistance, but terminated at a time equal to that achieved with expiratory resistance (isotime). The total decline in maximal isokinetic power at intolerance was apportioned to: 1) the power equivalent activation fatigue, and 2) the deficit in expected power at a given muscle activity (muscle fatigue). Additionally, the difference between the required constant power task and the instantaneous maximal isokinetic power at intolerance was measured. Inspiratory capacity and dyspnea were measured each minute. Expiratory flow limitation reduced exercise tolerance (487 ± 145 vs. 575 ± 137 s; p < 0.001), resulted in a greater decline in inspiratory reserve volume (0.19 ± 0.56 vs. 0.76 ± 0.54 L; p < 0.01), and increased dyspnea (8.5 ± 2 vs. 6.7 ± 2.5; p < 0.01). Muscle fatigue was unaffected at isotime (19 ± 34 vs. 17 ± 34 W; p > 0.05). Conversely, activation fatigue was greater at isotime with expiratory resistance (102 ± 76 vs. 127 ± 71 W; p < 0.05), and was related to the reduction in inspiratory reserve volume (r = -0.64, p < 0.05). Locomotor power reserve was smaller at isotime with expiratory resistance (253 ± 83 vs. 201 ± 92 W; p < 0.05). Dynamic hyperinflation and low inspiratory reserve volume exacerbated activation fatigue and reduced locomotor power reserve. Thus, imposed expiratory flow limitation initiates a cascade of abnormal lung mechanics and symptoms, which conflate to reduce exercise tolerance through limiting evocable motor power.