Branched-chain amino acids (BCAAs: leucine, isoleucine and valine) are essential amino acids for humans and animals. It has been shown that BCAA oxidation is promoted by exercise through activation of branched-chain α-keto acid dehydrogenase complex (BCKDC), which is a rate-limiting enzyme in the catabolic pathway of the BCAAs, and the elevated enzyme activity in skeletal muscle is quickly downregulated after exercise. This tight regulation of the BCKDC is consistent with stimulation of protein synthesis after exercise in skeletal muscle. With this background, it is interesting to consider the BCAAs as a supplement for sports. We conducted a human study to examine the effects of BCAA supplementation on the delayed-onset muscle soreness (DOMS) induced by squatting exercises. The results clearly showed that BCAA supplementation significantly reduced DOMS evaluated by a visual analog scale method and maintained leg muscle force during the period of DOMS. Other studies using different types of exercise support our findings, suggesting that BCAA supplements are useful for conditioning of skeletal muscle after exercise.