Intensively-reared white shrimp Litopenaeus vannamei are subjected to various environmental stresses that can have severe effects on their physiology. For example, low salinity stress decreases the activity of antioxidant enzymes. How to reduce the adverse effects of multiple environmental stresses on shrimp has become a new challenge in aquaculture. Chlorogenic acid has been documented to effectively scavenge free radicals and improve antioxidant defenses in humans and animals. The objectives of this study were to evaluate the effects of chlorogenic acid on the antioxidant system of L. vannamei, and determine whether it protects the shrimp against low salinity stress. A total of 360 shrimps with an average initial body weight of about 6.7 g were divided randomly into four replicated (×3) treatments, and reared indoors in 500-L glass-fiber tanks containing 300 L of natural seawater. The shrimp were fed one of four diets, a control diet without chlorogenic acid, and three diets containing different levels (100, 200, 400 mg/kg diet) of chlorogenic acid. Shrimps in each treatment were hand-fed one of the four diets to apparent satiation three times daily; uneaten food and feces were removed by siphoning. Prior to the beginning of the feeding trial, all shrimps were acclimatized for one week. Each tank was continuously oxygenated using an air pump, and 30% of the seawater was renewed daily. During the experimental period, water temperature, salinity, pH and other water quality parameters were kept stable. After being fed for 28 days, all shrimps were subjected to acute low salinity stress in which salinity was decreased rapidly from 32 to 10 for 72 h. The results indicated that at normal salinity (32), there were no significant differences in the survival, the total antioxidant status (T-AOC), superoxide dismutase (SOD) and catalase (CAT) activities of the hemolymph of white shrimps that were fed diets with or without chlorogenic acid. However, the glutathione peroxidase (GPx) activity and gene expression of GPx and CAT of shrimp hemolymph increased significantly (P<0.05) when shrimps were, for 14 days, fed diets containing different concentrations of chlorogenic acid. After exposure to low-salinity seawater for 24 h, survival of shrimps fed diets supplemented with chlorogenic acid increased by 10% compared with the control treatment, although the difference between the control and treatments was not significant (P>0.05). Activities of T-AOC, SOD and GPx of shrimp hemolymph in all treatments increased significantly after 24 h of low salinity stress, which suggests that low salinity induced an antioxidant stress response in the shrimps. Moreover, GPx and CAT activities of hemolymph in shrimp fed diets supplemented with chlorogenic acid were significantly higher than those fed the control diet after 24 h of low salinity stress (P<0.05). Over a period of 72 h of exposure to low salinity, activities of T-AOC, GPx and CAT, along with gene expression of GPx and CAT of hemolymph in white shrimp fed dietary chlorogenic acid, were significantly higher than those measured in the control animals. In conclusion, the findings of this study suggest that chlorogenic acid can serve as an effective antioxidant to regulate the antioxidant defense system of white shrimp and improve resistance against low salinity stress.