Infectious diseases cause considerable economic loss in aquaculture production due to virulent pathogens and various improper farm managements. Prevention is the only way to control disease incidence caused by viral pathogens. Use of antibiotics and chemicals in aquaculture is associated with several deleterious side effects. Vaccination is an effective tool in preventing and protecting cultured fish from virus diseases and controlling spread of diseases thereby contributing to sustainability of aquaculture sector. Therefore, the development of viral vaccines against emergent viral diseases is crucial for promoting successful aquaculture production. In this study, experimental recombinant major capsid protein (MCP) vaccine of similar damselfish virus was prepared and its efficacy was investigated in similar damselfish (Pomacentrus similis). The MCP gene of SRDV containing BamHI and XhoI as restriction sites was amplified from viral DNA with specific primer set and confirmed by agarose gel electrophoresis with the target size of 1416 bp. The gel purified PCR product was double digested with the said enzymes and ligated into pTriEx1.1 vector followed by transformation in E.coli DH5α. Plasmids from two clones namely pTriEx-MCP-1416-1 and pTriEx-MCP-1416-3 were transformed into E. coli BL21 (DE-3) pLacI. Two separate colonies obtained after transformation of pTriEx-MCP-1416-1 and pTriEx-MCP-1416-3 in E. coli BL21 (DE-3) pLacI were used for the expression of MCP gene. The crude protein mixture obtained from the colony of E. coli BL21 (DE-3) with expressed MCP inserts was used to assess the efficacy in similar damselfish by intra-peritoneal injection. After challenge with SRDV, damselfish immunized with recombinant protein showed the low level of protection with of relative percentage survival (RPS) value of 18.8% while vaccine added Quil-A® adjuvant showed RPS of 26%. Therefore, further investigations are required for the development of effective recombinant protein vaccine and assess its efficacy against SRDV challenge in marine fishes.