The present study reports the influence of salinity (5, 15, 25 and 35 g/L) on the biochemical and immune characteristics of Fenneropenaeus indicus challenged with 5. 5 × 104 copy number of white spot syndrome virus (WSSV). F. indicus that had been reared in 25 g/L, injected with WSSV and transferred to 5, 15, 25 (control) and 35 g/L were examined after 0–120 hrs for total hemocyte count (THC), phenoloxidase (PO) and respiratory burst (RB) activity and alkaline and acid phosphatase activities. It was concluded that F. indicus that had been transferred from 25 g/L to lower and higher salinity levels (5, 15 and 35 g/L) had poorer immune indices and decreased resistance against WSSV infection. After 120 hrs, the mortality rate in WSSV-injected F. indicus experimental groups (5 and 35 g/L) was significantly higher than for F. indicus exposed to 25 and 15 g/L salinities. During the experimental period (0–120 hrs), biochemical variables, namely total protein, carbohydrate, and lipid concentrations, were measured in hemolymph of both experimental and control groups. Acute salinity changes induced an increase in protein variations across the tested salinity ranges in shrimp. After 24 hrs, THC and PO activity decreased significantly whereas RB, alkaline phosphatase and acid phosphatase activities increased in shrimps kept at the lower salinities of 5, 15 and 35 g/L.