Marine environments are affected by large amounts of toxicants among those mercury (Hg). The aim of this study was to assess potential neurotoxic effects of Hg in the peacock blenny Salaria pavo. A sublethal contamination to 66 μg HgCl2 L−1 over periods of 1, 4, 10 and 15 days was performed. Total Hg concentrations measured in the brain highlighted the detection of Hg at days 1 and 4 following the exposure but no concentration of the metal was further detected. Partial-length cDNA of genes coding ABC transporters (abcb1, abcc1, abcc2, abcg2) and acetylcholinesterase (ache) were characterized. Results from mRNA expression levels displayed an up-regulation of abcb1 mRNA while a down-regulation of abcc1 and abcc2 mRNA was observed. No change in abcg2 and ache mRNA expression was noted throughout the experiment. At each sampling time, Hg exposure did not affect the activity of the AChE enzyme. The histological analysis indicated that fish exhibited several damages in the optic tectum and the cerebellum and 3 reaction patterns were identified for each organ: circulatory disturbances, regressive and progressive changes. Molecular, physiological and histological biomarkers assessed in the present study highlighted that peacock blennies were able to detoxify Hg from the brain tissue by developing defense mechanisms. More globally, neurotoxic effects of a sublethal Hg exposure in the brain of peacock blennies and the adaptation capacity of this species were evaluated.