Superoxide dismutase is a family of important antioxidant metalloenzymes and catalyzes the dismutation of toxic superoxide anions into dioxygen and hydrogen peroxide. A recent study identified the partial superoxide dismutase (SOD) gene in olive flounder (Paralichthys olivaceus). The same study reported that it strongly induced benzo[a]pyrene and that it was an indicator of aquatic oxidative stress responses. However, its transcriptional response against viral infection has not been investigated. In the present study, the spatial and temporal expression profiles were analyzed to investigate the function of Of-SOD in the antiviral response. The Of-SOD transcripts were ubiquitously detected at various levels in diverse tissues in a real-time PCR. The expression of Of-SOD was significantly higher in the muscles, liver, and brain but extremely low in the stomach and spleen. Following a VHSV challenge, the expression of Of-SOD increased within 3 h in the kidneys and decreased to the original level 2 days postchallenge. In muscle, liver, and brain, Of-SOD mRNA was similarly up-regulated at 3-6 h postchallenge and then decreased to the basal level. Although the expression pattern and induction time differed slightly depending on the tissue, the transcript of Of-SOD consistently increased in the acute infection response, but the expression was low in the chronic response. The expression of Of-SOD was induced after the VHSV infection, and Of-SOD was probably involved in the immune response against the viral challenge. These results suggest that SOD may play important roles in the immune defense system of P. olivaceus and perhaps contribute to the protective effects against oxidative stress in olive flounder.