The aim of this study was to examine the effect of low muscle glycogen on the neuromuscular responses to maximal eccentric contractions. Fourteen healthy men (22 ± 3 years) performed single-leg cycling (20 min at ∼75% maximal oxygen uptake (VO2 max); eight 90 s sprints at a 1:1 work-to-rest ratio (5% decrements from 90% to 55% max until exhaustion) the evening before 100 eccentric (1.57 rad s−1) with reduced (RED) and normal glycogen (NORM). Neuromuscular responses were measured during and up to 48 h after with maximal voluntary and involuntary (twitch, 20 Hz and 50 Hz) isometric contractions. During eccentric contractions, peak torque decreased (RED: −16.1 ± 2.5%; NORM: −6.2 ± 5.1%) and EMG frequency increased according to muscle length. EMG activity decreased for RED only. After eccentric contractions, maximal isometric force was reduced up to 24 h for NORM (−13.5 ± 5.8%) and 48 h for RED (−7.4 ± 10.9%). Twelve hours after eccentric contractions, twitch force and the 20:50 Hz ratio were decreased for RED but not for NORM. Immediate involuntary with prolonged voluntary force loss suggests that reduced glycogen is associated with increased susceptibility to mild muscle-damaging eccentric exercise with contributions of peripheral and central mechanisms to be different during recovery.