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Omega-3 ( n -3) polyunsaturated fatty acids (PUFAs) have been known to exert anti-inflammatory effects on various disease states. However, its effect on CD8 + T cell-mediated immunopathology upon viral infection has not been well elucidated yet. In this study, we investigated the possible implication of n -3 PUFAs in CD8 + T cell responses against an acute viral infection. Infection of FAT-1 transgenic mice that are capable of synthesizing n -3 PUFAs from n -6 PUFAs with lymphocytic choriomeningitis virus (LCMV) resulted in significant reduction of anti-viral CD8 + T cell responses. Interestingly, expansion of adoptively transferred wild-type (WT) LCMV-specific T cell receptor (TCR) transgenic CD8 + (P14) T cells into FAT-1 mice was significantly decreased. Also, activation of anti-viral CD4 + helper T cells was reduced in FAT-1 mice. Importantly, P14 cells carrying the fat-1 gene that were adoptively transferred into WT mice exhibited a substantially decreased ability to proliferate and produce cytokines against LCMV infection. Together, n -3 PUFAs attenuated anti-viral CD8 + T cell responses against an acute viral infection and thus could be used to alleviate immunopathology mediated by the viral infection.