Therapeutic drug monitoring of antiepileptic drugs is based on patient serum samples. In this study, we evaluated the correlation between lacosamide (LCM) steady state concentrations in serum and saliva samples. Additionally, we investigated the relation with daily dose, and assessed the feasibility of saliva collection. This was an open-label, single center study including data from 25 patients at the Bethel Epilepsy Center treated with LCM (50-650 mg/d). Samples were collected in the morning (fasting values) and in selected cases at 50 minutes to 5 hours after the morning dose. Nonsignificant differences in the mean LCM morning (trough) concentration in serum and saliva were observed. Serum and saliva concentrations across all samples were highly correlated, (r = .874), with a slightly lower correlation when only fasting values were analyzed (r = .860). Higher correlation with daily dosages was observed in serum samples (r = .773) than in saliva samples (r = .604). Serum and saliva concentrations increased significantly after intake of the LCM morning dose (P < .001). The median absolute and percentage increase of LCM in serum were moderately lower than in saliva samples, with a few outliers in saliva samples. Consequently, saliva could offer great clinical potential to monitor drug concentrations and guide LCM treatment in epileptic patients.