This study tested the relationship between the magnitude of muscle damage and both central and peripheral modulations during and after eccentric contractions of plantar flexors. Eleven participants performed 10 sets of 30 maximal eccentric contractions of the plantar flexors at 45 • ·s −1. Maximal voluntary torque, evoked torque (peripheral component) and voluntary activation (central component) were assessed before, during, immediately after (POST) and 48 h after (48 h) the eccentric exercise. Voluntary eccentric torque progressively decreased (up to −36%) concomitantly to a significant alteration of evoked torque (up to −34%) and voluntary activation (up to −13%) during the exercise. Voluntary isometric torque (−48 ± 7%), evoked torque (−41 ± 14%) and voluntary activation (−13 ± 11%) decreased at POST, but only voluntary isometric torque (−19 ± 6%) and evoked torque (−10 ± 18%) remained depressed at 48 h. Neither changes in voluntary activation nor evoked torque during the exercise were related to the magnitude of muscle damage markers, but the evoked torque decrement at 48 h was significantly correlated with the changes in voluntary activation (r = −0.71) and evoked torque (r = 0.77) at POST. Our findings show that neuromuscular responses observed during eccentric contractions were not associated with muscle damage. Conversely, central and peripheral impairments observed immediately after the exercise reflect the long-lasting reduction in force-generating capacity.