Thrombospondins (TSPs) are extracellular, calcium-binding glycoproteins that play an essential role in cell homeostasis and development, wound-healing, angiogenesis, connective tissue organization, immune response etc. and it conserves from sea sponges to mammals. However, their role in shrimp immunity is poorly understood. In the present study, the differential expression profiling of TSP transcripts in Penaeus monodon tissues such as gills, lymphoid organs, hepatopancreas, and hemolymph challenged with white spot syndrome virus (WSSV), were studied by quantitative real-time PCR. Further, shrimps fed with the immunostimulant (β-glucan) when challenged with WSSV showed significant upregulation of TSP expression in gills, hepatopancreas, and lymphoid organ at the early phase of WSSV infection. The results suggest that TSP may be an inducible acute phase response protein to WSSV infection. The possibility of differences in mRNA expression pattern seen in immunostimmulated shrimp after the viral challenge, possibility due to altered immune mechanisms getting triggered during immunostimulant administration and virus infections in the host.