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Ammonia is one of the major environmental pollutants that affect the growth and physiological functions of organisms. In the present study, the effects of ammonia on the immune response and pathogen resistance of mud crab reovirus (MCRV) in mud crab were investigated. Mud crab were exposed to four different ammonia concentrations (0, 2.5, 5 and 10 mg L-1 ammonia-N) for 7 d. The result showed that aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity significantly increased after 5 and 10 mg L-1 ammonia exposure. The hepatopancreas superoxide dismutase (SOD), catalase (CAT), and total antioxidative capacity (T-AOC) in ammonia-N group were significantly lower than those in the control group, while the levels of malondialdehyde (MDA) were significantly higher than those in the control group. Significant reductions in total hemocyte counts (THC) were observed after ammonia exposure. After 7d ammonia exposure, mud crabs were injected 100 μL MCRV at 105 copies/g body weight. The mortality of mud crabs in ammonia-N group were significantly higher than those in the control group. All these results suggested that ammonia in water caused a depression in the immune response, and increased susceptibility to MCRV infection.