Currently the most common and devastating disease of shrimp is caused by the white spot syndrome virus (WSSV), which has spread throughout the world mainly by different species of crustaceans carrying the virus. Penaeus monodon were challenged with WSSV and the protein expression variation studied over a period of time. The gills, one of the main target organs of WSSV, showed upregulation of 24 proteins and expression of three novel proteins after infection. In the hepatopancreas, 20 upregulated proteins and six novel proteins were observed. The muscle showed upregulation of 11 proteins and one new protein. Subcellular organelles like nuclear and mitochondrial proteins of each tissue showed different profiles with either increased/decreased expression of few proteins or additional expression of novel proteins. The protein profiles resolved in the study provide a rich source of information on proteins in shrimp which may be involved in antiviral response.