This study evaluated the effectiveness of low-load resistance training with a blood flow restriction (LL(BFR)) to attenuate muscle loss and weakness after 30 days of unilateral lower limb suspension (ULLS). Sixteen subjects (ages 18-50 yr) underwent 30 days of ULLS. Measurements of muscle strength, cross-sectional area, and endurance on the knee extensors and plantar flexors were collected before and after ULLS. Plasma concentrations of IGF-1 and IGFBP-3 were also assessed. During ULLS, eight subjects (5 males, 3 females) participated in LL(BFR) three times per week (ULLS + Exercise) while eight subjects (4 males, 4 females) did not exercise (ULLS). The blood flow-restricted exercise consisted of dynamic knee extension at 20% of the subject's isometric maximum voluntary contraction coupled with a suprasystolic blood flow restriction. After 30 days of limb suspension, the ULLS + Exercise group experienced minimal and insignificant losses in knee extensor cross-sectional area and strength (1.2% and 2.0%, respectively; P = 0.05), while the ULLS group demonstrated significant reductions in cross-sectional area and strength (7.4% and 21%, respectively). Decrements in plantar flexor strength (23.7%) and cross-sectional area (7.4%) were observed after ULLS (P < 0.05) and were of similar magnitude between the experimental groups (P > 0.05). Muscular endurance in the knee extensors improved 31% in the ULLS + Exercise group, while it decreased 24% in the ULLS group (P = 0.01). No changes were seen in hormone concentrations throughout the study. In conclusion, LL(BFR) of the knee extensors is effective in maintaining muscle strength and size during 30 days of ULLS and results in improved knee extensor muscular endurance.