Purpose <p>To determine the effect of the total creatine (tCr) and accessible phosphate (aP) pool (tCaP) on the kinetic variables (maximal muscle oxygen consumption, V̇O_2max, transition time of the muscle V̇O₂ on-kinetics, t_0.63, time to exhaustion, t_lim, critical power, CP and work over CP in the power-duration relationship, W’) of intense moderate-term endurance exercise.</p> Methods <p>A dynamic computer model of the skeletal muscle bioenergetic system, involving the each-step-activation mechanism of system stimulation during work transitions and P_i-double-threshold mechanism of muscle fatigue is used.</p> Results <p>A decrease in tCaP significantly increases V̇O_2max, t_lim and CP, moderately increases W’ and shortens t_0.63. Significantly enough decrease in tCaP moves the system (at a determined power output) from the severe to heavy (and further to moderate) exercise intensity domain. An increase in tCr alone has an insignificant effect on the system.</p> Conclusions <p>A decrease in tCaP, especially in aP, increases fatigue resistance of muscle during endurance exercise through attenuation of P_i increase during exercise. An increase in tCr alone has little impact on fatigue resistance. In the sequence of muscle cell types: glycolytic fast-twitch type II skeletal muscle fibers → oxidative slow-twitch type I skeletal muscle fibers → heart muscle fibers the tCaP, especially aP, pool size decreases, which can contribute to the increasing fatigue-resistance in this sequence. While Cr supplementation, elevating tCr, increases the strength and force of acute maximal-intensity very-short-term exercise, it has no significant effect on endurance exercise, at least through the creatine kinase system.</p>