Cisplatin (CDDP) induces loss of muscle mass by activating the nuclear factor (NF)-κB signaling pathway. In this study, we investigated the effects of eicosapentaenoic acid (EPA), which inhibits NF-κB activation, on CDDP-induced loss of muscle mass in mice.Male C57BL/6J mice received a single dose of CDDP and olive oil, linseed oil, or EPA daily for 4 days. Body weight and food intake were recorded daily for 5 days. Forelimb grip strength was determined using a strain gauge on the fourth day. The mice were killed 24 h after the final dose of fatty acid and the wet weight of their gastrocnemius, soleus, and tibialis anterior muscles measured.Olive oil, linseed oil, and EPA all failed to prevent decrease in food intake and loss of body weight. However, only EPA prevented loss of muscle mass and strength.EPA prevents CDDP-related loss of muscle mass and muscle but not CDDP-related loss of body weight.