Oligonol, a phenolic production from lychee, has been reported to exhibit anti-oxidative and anti-inflammatory effects. This study investigated the effect of Oligonol supplementation on circulating levels of prostaglandin $E_2$ ($PGE_2$) and cyclooxygenase (COX)-2, as well as body temperature, after heat stress in 17 healthy human male volunteers (age, $21.6{pm}2.1$ years). All experiments were performed in an automated climate chamber ($26.0^{circ}C{pm}0.5^{circ}C$, relative humidity $60%{pm}3.0%$, air velocity less than 1 m/sec) between 2 and 5 p.m. Subjects ingested an Oligonol (100 mg)-containing beverage or placebo beverage before half-body immersion into hot water ($42^{circ}C{pm}0.5^{circ}C$ for 30 min). Tympanic and skin temperatures were measured and mean body temperatures were calculated. Serum concentrations of $PGE_2$ and COX-2 were analyzed before, immediately after, and 60 min after immersion. Oligonol intake significantly prevented elevation of tympanic (temperature difference: $0.17^{circ}C$ at Post, P < .05; $0.17^{circ}C$ at Re-60, P < .05) and mean body temperatures (temperature difference: $0.18^{circ}C$ at Post, P < .05; $0.15^{circ}C$ at Re-60, P < .05), and lowered concentrations of serum $PGE_2$ (increased by 13.3% vs. 29.6% at Post, P < .05) and COX-2 (increased by 15.6% vs. 21.8% at Post, P < .05), compared to placebo beverage. Our result suggests that Oligonol has the potential to suppress increases in body temperature under heat stress, and this is associated with decreases in serum levels of $PGE_2$ and COX-2.