<jats:p>Chitosan oligosaccharides (COS) exhibits antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the effects of COS on antioxidant system and inflammatory response in heat-stressed rats. A total of 30 male rats were randomly divided to three groups and reared at either 24 °C or 35 °C for 4 h/d for this 7-day experiment: CON, control group with basal diet; HS, heat stress group with basal diet; HSC, heat stress with 200mg/kg COS supplementation. Compared with the CON group, HS significantly decreased (p < 0.05) average daily gain (ADG); average daily feed intake (ADFI); the relative weight of spleen and kidney; the level of liver CAT, GSH-Px, T-AOC, and IL-10; spleen SOD, GSH-Px, GSH, and IL-10; and kidney SOD, GSH-Px, T-AOC, and IL-10, while significantly increased the MDA concentration in liver, spleen, and kidney; the liver IL-1β concentration; and spleen and kidney IL-6 and TNF-α concentration. In addition, dietary COS supplementation significantly improved (p < 0.05) ADG; the relative weight of spleen and kidney; the level of liver GSH-Px, spleen GSH-Px, GSH, and IL-10; and kidney GSH-Px, while significantly decreased (p < 0.05) liver IL-1β concentration under heat stress condition. Collectively, COS was beneficial to heat-stressed rats by alleviating oxidative damage and inflammatory response.</jats:p>