A sensitive and accurate gas chromatography-mass spectrometric method was developed and validated for the simultaneous determination of levetiracetam and lamotrigine in whole blood. A solid-phase extraction (SPE) procedure using HF Bond Elut C18 columns followed by derivatization using N-methyl-N-tert-butyldimethylsilyl-trifluoroacetamide (MTBSTFA) with 1% tert-butyldimethylsilyl chloride (TBDMSCl) was used. In this assay, levetiracetam-d6 was used as internal standard. Limits of detection and quantification were 0.15 and 0.50 μg/mL, respectively, for both analytes. The method was proved to be linear within the concentration range of 0.50-50.0 μg/mL (R(2) ≥ 0.992) for both analytes. Absolute recovery was found to be at least 90.0 and 97.2% for levetiracetam and lamotrigine, respectively. Intra-day and inter-day accuracy values for both analytes were ranged from -6.5 to 4.2 and -6.6 to 3.0%, respectively, whereas their respective precision values were less than 11.4 and 8.3%. The developed method was successfully used in our laboratory for quantification of levetiracetam and lamotrigine blood concentrations during the investigation of forensic cases where these antiepileptic drugs were involved. This method could also be used for therapeutic drug monitoring purposes.