Several results have suggested that coenzyme Q10 has protective effects in different models of epilepsy. This study was designed to investigate the acute effect of coenzyme Q10 in genetic absence epileptic WAG/Rij rats. We also determined the role of L-arginine (L-Arg), a biological precursor of nitric oxide (NO), and 7-nitroindazole (7-NI), an inhibitor of neuronal NO synthase (nNOS), on the effects of coenzyme Q10. Electrocorticography (ECoG) recordings were obtained during the 180 min after the administration of the different doses of coenzyme Q10 (25, 50, 100 and 200 mg/kg), L-Arg (500 and 1000 mg/kg), 7-NI (25 and 50 mg/kg) or the combinations of coenzyme Q10 (100 mg/kg) with L-Arg (1000 mg/kg) or 7-NI (50 mg/kg). The total number of spike wave discharges (SWDs) and the mean duration of SWDs were calculated and compared. Coenzyme Q10, at the doses of 50 mg/kg, increased the total number of SWDs but did not changed the mean duration of SWDs. Coenzyme Q10 (100 and 200 mg/kg) or L-Arg (500 and 1000 mg/kg) increased both the total number and the mean duration of SWDs. In contrast, the administration of 7-NI (25 and 50 mg/kg) decreased the total number of SWDs and the mean duration of SWDs. Coadministration of L-Arg enhanced the effect of coenzyme Q10 on the total number of SWDs but not on the mean duration of SWDs. Moreover, the coadministration of 7-NI abolished the effect of coenzyme Q10 on both SWD parameters. The electrophysiological evidences from this study suggest that administration of coenzyme Q10 increases absence seizures by stimulating the synthesis of neuronal NO.