Pareja-Blanco, F, Rodríguez-Rosell, D, Aagaard, P, Sánchez-Medina, L, Ribas-Serna, J, Mora-Custodio, R, Otero-Esquina, C, Yáñez-García, JM, and González-Badillo, JJ. Time course of recovery from resistance exercise with different set configurations. J Strength Cond Res XX(X): 000-000, 2018-This study analyzed the response to 10 resistance exercise protocols differing in the number of repetitions performed in each set (R) with respect to the maximum predicted number (P). Ten males performed 10 protocols (R(P): 6(12), 12(12), 5(10), 10(10), 4(8), 8(8), 3(6), 6(6), 2(4), and 4(4)). Three sets with 5-minute interset rests were performed in each protocol in bench press and squat. Mechanical muscle function (countermovement jump height and velocity against a 1 m·s load, V1-load) and biochemical plasma profile (testosterone, cortisol, growth hormone, prolactin, IGF-1, and creatine kinase) were assessed at several time points from 24-hour pre-exercise to 48-hour post-exercise. Protocols to failure, especially those in which the number of repetitions performed was high, resulted in larger reductions in mechanical muscle function, which remained reduced up to 48-hour post-exercise. Protocols to failure also showed greater increments in plasma growth hormone, IGF-1, prolactin, and creatine kinase concentrations. In conclusion, resistance exercise to failure resulted in greater fatigue accumulation and slower rates of neuromuscular recovery, as well as higher hormonal responses and greater muscle damage, especially when the maximal number of repetitions in the set was high.