The purpose of the present study was to examine the effects of daily administration of two different arginine-based supplements for four weeks on the physical working capacity at the fatigue threshold (PWCFT). The PWCFT test estimates the highest power output that can be maintained without neuromuscular evidence of fatigue. The study used a double-blind, placebo-controlled design. Fifty college-aged males (mean age ± SD = 23.9 ± 3.0) were randomized into one of three groups: 1) placebo (n = 19); 2) 1.5 gm arginine (n = 14); or 3) 3.0 gm arginine (n = 17). The placebo was microcrystalline cellulose. The 1.5 gm arginine group ingested 1.5 gm of arginine and 300 mg of grape seed extract, whereas the 3.0 gm arginine group ingested 3.0 gm of arginine and 300 mg of grape seed extract. All subjects performed an incremental test to exhaustion on a cycle ergometer prior to supplementation (PRE) and after 4 weeks of supplementation (POST). Surface electromyographic (EMG) signals were recorded from the vastus lateralis using a bipolar electrode arrangement during the incremental tests for the determination of the PRE and POST supplementation PWCFT values. There were significant mean increases (PRE to POST) in PWCFT for the 1.5 gm (22.4%) and 3.0 gm (18.8%) supplement groups, but no change for the placebo group (−1.6%). These findings supported the use of the arginine-based supplements for improving neuromuscular performance and delaying the onset of fatigue during cycle ergometry.