In order to investigate the underlying mechanisms of methylmecury (MeHg)-mediated toxicity to Atlantic cod (Gadus morhua), we analyzed the liver proteome of fish exposed in vivo to MeHg (0, 0.5, 2 mg/kg body weight) for 2 weeks. Label-free quantitative mass spectrometry enabled quantification of 1143 proteins, and 125 were differentially regulated between MeHg-treated samples and controls. Six proteins among the top differentially regulated (T23O, GLNA EPS8L2, APOA4, RAP1B, CZTZ) were analyzed using selected reaction monitoring (SRM). Supported by bioinformatics analyses, we conclude that MeHg disrupts mainly redox homeostasis and energy generating metabolic pathways in cod liver, the latter potentially modulated through MeHg-induced oxidative stress.