The presence of microplastics and several other pollutants in the marine environment is of growing concern. However, the knowledge on the toxicity of mixtures containing microplastics and other contaminants to marine species is still scarce. The main goals of this study were to investigate the oxidative stress and lipid oxidative damage potentially induced by 96 h of exposure to mercury (0.010 and 0.016 mg/L), microplastics (0.26 and 0.69 mg/L), and mixtures of the two substances (same concentrations, full factorial) in the gills and liver of D. labrax juveniles, and the possible influence of microplastics on mercury bioconcentration (gills) and bioaccumulation (liver). The results indicate that the presence of microplastics in the water increased the concentration of mercury in gills and liver of D. labrax juveniles. Microplastics and mercury, alone and in mixtures, caused oxidative stress in both organs. Based on the total induction of antioxidant enzymatic activity, the type of toxicological interaction in fish exposed to the mixture containing the lowest concentration of the two substances was addition in gills, and addition or synergism in the liver. These results stress the need to further address the role of microplastics in the bioconcentration, bioaccumulation, and toxicity of other environmental contaminants in different species.