Purpose: Peripheral and central factors play important roles in the reduction of motor performance following damaging eccentric exercise and delayed onset muscle soreness (DOMS). Following this regime, contralateral limbs could also be affected; however, the factors involved remain inconclusive. The purpose of this study was to distinguish the peripheral and central factors following eccentric contraction and DOMS of the plantar flexors in treated and contralateral homologous limbs. Methods: Ten males (BMI = 25.08 ± 1.69kgm-2; age = 28.70 ± 4.24 years) were randomly assigned to experimental (DOM) or control (CON) groups. The DOM group performed a damaging eccentric exercise, while the CON group rested. Plasma creatine kinase (CK), pain rating scale (PRS), muscle stiffness, maximal voluntary contraction (MVC), and neural voluntary activation (VA) were measured before, after 10 min, and after 24, 48, and 72 hr on treated and contralateral limbs. Results: Following exercise, CK increased until after 48 hr, while PRS increased until after 72 hr compared to the CON group. Importantly, MVC was reduced at all time points, with the greatest reduction observed after 24 hr (-16%), while VA was affected until after 48 hr, with the greatest reduction at after 10 min (-7%). Interestingly, a "cross-over effect" was observed in contralateral limbs when PRS, MVC, and VA were negatively affected following the same pattern (time line) as treated limbs (-13% peak MVC reduction; -3.5% peak VA reduction). Conclusion: These findings suggest a substantial central contribution to the reduction in force immediately following eccentric exercise and to a lesser extent during the latter part of DOMS in both treated and contralateral limbs.