[Purpose] This study aimed to investigate the effects of leucine-enriched essential amino acid (LEAA) supplementation on muscle fatigue and the level of inflammatory cytokines in wheelchair basketball players after a basketball game and interval training. [Methods] Of the ten recruited wheelchair basketball players (aged 34.5±8.9 years; lean body mass of 34.3±10.0 kg) who had spinal cord injury (SCI) and had undergone amputation, nine participated in the final test. These nine athletes received LEAA supplements (3 times 4.0 g/day) or placebo treatment in a double-blind, randomized, crossover study. We measured variables related to muscular fatigue and inflammatory response before the intense exercise and 4 days after recovery. [Results] The significant effect of LEAA supplementation was inhibition of circulating IL-6 levels in the LEAA-treated group compared with the placebo group (P < .05). However, no changes were observed in the TNF-α and creatinine kinase levels. Moreover, analysis of variance analysis showed no significant difference in the relative values of muscle soreness. However, the effect size analysis with Cohen’s d reported a significant improvement in the relative values of whole body and back muscle soreness. [Conclusion] Our results revealed that LEAA supplementation before and after intense exercise could help reduce muscle soreness and IL-6 levels in wheelchair basketball players.