During the production of desalination plants, concentrated seawater is expelled to local marine environments, which may lead to hypersaline pollution. To assess environmental risk of hypersalinity, Crassostrea angulate, Scylla paramamosain and Epinephelus akaara were exposed to salinities of 30‰, 36‰ and 40‰, then changes of serum nonspecific immune indices were monitored for 96 hours, including superoxide dismutase (SOD) and acid phosphatase (ACP) activity, and contents of serum total protein and albumin. Two-way ANONA revealed that salinity only affected contents of serum total protein and albumin in C. angulate, and content of serum albumin in S. paramamosain and content of serum total protein in E. akaara. Compared with the control, hypersaline treatments (36‰ and/or 40‰) first increased contents of serum total protein and albumin and then decreased them in C. angulate, suppressed content of serum albumin in S. paramamosain, and increased content of serum total protein in E. akaara. These results suggested that exposure to hypersalinity might enhance innate immunity of C. angulate and E. akaara, but suppressed it in S. paramamosain.