Background <p>Oxidative damage has been implicated in multiple neurodegenerative diseases, including epilepsy. Selenium, in the form of selenoproteins is an integral part of the human antioxidant defense system. Though a relationship between the altered selenium levels and epilepsy has been reported, limited evidence is available about the expression pattern of selenoproteins in epileptic patients.</p> Objective <p>This study aimed to determine the serum selenium levels in idiopathic epileptic and healthy individuals. Expression profiling of selenoproteins (GPx1, TRxR1 and SEPW1) both at mRNA and protein levels was also evaluated.</p> Methods <p>Serum selenium levels of 30 patients with idiopathic generalized epilepsy and their age and gender matched 30 healthy controls were measured. Protein levels of Serum Glutathione Peroxidase 1 (GPx1), Thioredoxin Reductase 1 (TRxR1) and Selenoprotein W (SEPW1) were estimated using ELISA. mRNA expression of GPx1, TRxR1 and SEPW1 were determined using qRT-PCR.</p> Results <p>The mean values for serum selenium levels in cases and controls were 37.6 <Emphasis Type="Underline">±</Emphasis> 2.0 µmol/ml and 38.9 <Emphasis Type="Underline">±</Emphasis> 2.7 µmol/ml, respectively. Selenium levels in cases were significantly lower as compared to controls (<i>p</i> = 0.031). No statistically significant differences were observed between the serum levels of selenoproteins GPx1, TRxR1 and SEPW1 in epileptic patients and the healthy group. GPx1 and TRxR1 expression was found to be down regulated (0.34 and 0.13 folds respectively) whereas SEPW 1 was found to be 0.04 folds up regulated in epileptic patients compared to the healthy subjects.</p> Conclusion <p>Selenium deficiency observed in epileptic patients suggests the association between serum selenium levels and epilepsy. This study provides the information about the selenium status in Pakistani population and helps in understanding the role of selenium in the prevention of epilepsy.</p> Graphical Abstract <p></p>