PURPOSE: The aim of the study is to evaluate central and peripheral neuromuscular function in the knee extensors (KE) and plantar flexors (PF) after 30 days of unilateral lower limb suspension (ULLS) and to examine the effects of low-load blood flow restricted (BFR) resistance training on the KE during ULLS. METHODS: Strength, cross-sectional area (CSA), central activation, evoked force, and rates of force development and relaxation were assessed in the KE and PF before and after ULLS in sixteen subjects (9 M, 7F; 18-49 years). Eight of those subjects participated in BFR on the KE three times per week during ULLS (ULLS + Exercise). RESULTS: The ULLS group had decrements in strength and CSA of the KE (16 and 7 %, respectively) and PF (27 and 8 %, respectively) and the ULLS + Exercise maintained strength and CSA of the KE (P > 0.05), but significantly lost strength and CSA in the PF (21 and 5 %; P > 0.05). KE central activation declined 6 % in the ULLS group and was maintained in the ULLS + Exercise group, but a time × group interaction was not evident (P = 0.31). PF central activation was reduced in both groups (ULLS: -7.6 ± 9.9 and -7.9 ±11.6 %; time main effect P = 0.01). A time × group interaction for KE-evoked twitch force (P = 0.04) demonstrated a 9 % decline in the ULLS + Exercise group following the intervention. Evoked PF doublet torque decreased 12 % in both groups (P = 0.002). CONCLUSION: Central and peripheral neuromuscular function is compromised during unloading. While BFR resistance training on the KE during unloading can maintain muscle mass and strength, it may only partially attenuate neuromuscular dysfunction.