On on an indoor track at a constant velocity corresponding to 95% of the velocity associated with the maximal oxygen uptake (mean ± SD = 5.1 ± 0.3 m·s−1, time to exhaustion = 10.7 ± 2.6 min). Vertical and horizontal ground reaction forces were measured every lap (200 m) by a 5-m-long force platform system. Cr was measured from pulmonary gas exchange using a breath-by-breath portable gas analyzer. Results: Leg stiffness (−13.1%, P < 0.05) and peak vertical (−9.2%, P < 0.05) and propulsive (−7.5%, P < 0.001) forces decreased significantly with fatigue, whereas vertical stiffness did not change significantly. Leg and vertical stiffness changes were positively related with modifications of aerial time (R2 = 0.66, P < 0.01 and R2 = 0.72, P < 0.01, respectively) and negatively with contact time (R2 = 0.71, P < 0.01 and R2 = 0.74, P < 0.01, respectively). Alterations of vertical forces were related with the decrease of the angle of velocity vector at toe off (R2 = 0.73, P < 0.01). When considering mean values of oxygen uptake, no change was observed from 33% to 100% of the time to exhaustion. However, between one-third and two-thirds of the fatiguing run, negative correlations were observed between oxygen consumption and leg stiffness (R2 = 0.83, P < 0.001) or vertical stiffness (R2 = 0.50, P < 0.03). Conclusions: During a constant run to exhaustion, the fatigue induces a stiffness adaptation that modifies the stride mechanical parameters and especially decreases the maximal vertical force. This response to fatigue involves greater energy consumption....