Mercury (Hg) concentrations have increased in western Arctic beluga whales (Delphinapterus leucas) since the industrial revolution. Methylmercruy (MeHg) is a known neurotoxicant, yet little is known about the risk of exposure for beluga whales. Selenium (Se) has been linked to demethylation of MeHg in cetaceans, but its role in attenuating Hg toxicity in beluga whales is poorly understood. The objective of this study is to explore relationships between Hg and Se concentrations and neurochemical biomarkers in different brain regions of beluga whales in order to assess potential neurotoxicological risk of Hg exposure in this population. Brain tissue was sampled from hunter-harvested beluga whales from the western Canadian Arctic in 2008 and 2010. Neurochemical and molecular biomarkers were measured with radioligand binding assays and quantitative PCR, respectively. Total Hg (HgT) concentration ranged from 2.6-113 mg kg(-1) dw in temporal cortex. Gamma-amminobutyric acid type A receptor (GABAA-R) binding in the cerebellum was negatively associated with HgT, MeHg and total Se (SeT) concentrations (p ≤ 0.05). The expression of mRNA for GABAA-R subunit α2 was negatively associated with HgT and MeHg (p ≤ 0.05). Furthermore, GABAA-R binding was positively correlated to mRNA expression for GABAA-R α2 subunit, and negatively correlated to the expression of mRNA for GABAA-R α4 subunit (p ≤ 0.05). The expression of N-methyl-d-aspartate receptor (NMDA-R) subunit 2b mRNA expression was negatively associated with iHglabile concentration in the cerebellum (p ≤ 0.05). Variation of molecular and/or biochemical components of the GABAergic and glutamatergic signaling pathways were associated with MeHg exposure in beluga whales. Our results show that MeHg exposure is associated with neurochemical variation in the cerebellum of beluga whales and Se may partially protect from MeHg-associated neurotoxicity.