N-3 polyunsaturated fatty acids (PUFA), derived from marine oils, have been shown to protect against various neurological diseases. However, very little is known about their potential anticonvulsant properties. The objective of the present study was to determine whether enrichment of brain lipids with n-3 PUFA inhibits seizures induced by pentylenetetrazol. We demonstrate that increased brain levels of n-3 PUFA in transgenic fat-1 male mice, which are capable of de novo synthesis of n-3 PUFA from n-6 PUFA, increases latency to seizure onset by 45%, relative to wildtype controls (p = 0.08). Compared with wildtype littermates, transgenic fat-1 mice have significantly (p < 0.05) higher levels of docosahexaenoic acid and total n-3 PUFA in brain total lipid extracts and phospholipids. Levels of brain docosahexaenoic acid were positively correlated to seizure latency (p < 0.05). These findings demonstrate that n-3 PUFA have anticonvulsant properties and suggest the possibility of a novel, non-drug dietary approach for the treatment of epilepsy.