Mercury (Hg), one of the elements most toxic to biota, accumulates within organisms throughout their lifespan and biomagnifies along trophic chain. Due to their key role in marine systems, cephalopods constitute a major vector of Hg in predators. Further, they grow rapidly and display complex behaviours, which can be altered by neurotoxic Hg. This study investigated Hg concentrations within 81 cephalopod specimens sampled in the Bay of Biscay, which belonged to five species: Eledone cirrhosa, Sepia officinalis, Loligo vulgaris, Todaropsis eblanae and Illex coindetii. Hg concentrations were measured in the digestive gland, the mantle muscle and the optic lobes of the brain. The digestive gland and the mantlewere tissueswith themost concentrated Hg among all species considered (up to 1.50 μg.g−1 dw), except E. cirrhosa. This benthic cephalopod had 1.3-fold higher Hg concentrations in the brain (up to 1.89 μg.g−1 dw) than in the mantle, while other species had 2-fold lower concentrations of Hg in the brain than in the mantle. Brain-Hg concentrations can be predicted from muscle-Hg concentrations for a given species, which facilitates the assessment of Hg toxicokinetics in cephalopods. In the most contaminated E. cirrhosa individual, the chemical form of Hg in its digestive gland, mantle muscle and optic lobes, was determined using High energy-Resolution X-ray Absorption Near Edge Structure (HR-XANES) spectroscopy. In the digestive gland, 33 ± 11% of total Hg was inorganic Hg speciated as a dicysteinate complex (Hg(Cys)2), which suggested that the demethylation of dietary MeHg occurs in this organ. All Hg found in the mantle muscle and the optic lobes is methylated and bound to one cysteinyl group (MeHgCys complex), which implies that dietary MeHg is distributed to these tissues via the bloodstream. These results raised the questions regarding interspecific differences observed regarding Hg brain concentrations and the possible effect of Hg on cephalopod functional brain plasticity and behaviour.