To compare the levels of plasma glutamate and glutamine in drug-resistant or drug-responsive symptomatic focal epilepsy. Dysfunctional glutamate neurotransmission plays an essential role in epilepsy pathophysiology.This cross-sectional study included 80 drug-resistant and 42 drug-responsive symptomatic focal epileptic patients and 132 healthy controls from June 2017 to February 2018. Plasma glutamate and glutamine levels were assessed via high-performance liquid chromatography.Patients with drug-resistant symptomatic focal epilepsy had significantly higher plasma glutamate levels than healthy controls, whereas those with the drug-responsive disease had higher plasma glutamine levels than healthy controls. These results indicate that plasma glutamate and glutamine levels can discriminate patients with drug-resistant and drug-responsive symptomatic focal epilepsy from control individuals with the areas under the curve values of 0.931 and 0.72, respectively.Elevated plasma glutamate levels are associated with drug-resistant symptomatic focal epilepsy and may aid the diagnosis of drug-resistant symptomatic focal epilepsy.Copyright: © Neurosciences.