Metacercariae of Cryptocotyle are among the most numerously recorded trematode parasites in the estuarine biocenoses of the Azov-Black Sea basin. These parasites can massively affect body surface, gills and fins of host fishes including gobiids. However, information on the influence of Cryptocotyle metacercariae on the physiological and biochemical status of gobies is extremely limited. Biochemical response of two fish species of Gobiidae - grass goby Zosterisessor ophiocephalus (Pallas, 1814) and mushroom goby Ponticola eurycephalus (Kessler, 1874) to Cryptocotyle spp. metacercariae infection at the mouth of River Chernaya (Black Sea) was investigated. Activities of superoxide dismutase, catalase, peroxidase, glutathione reductase, glutathione-S-transferase, alanine transaminase, aspartate transaminase, level of thiobarbituric acid-reactive substances were measured as parameters of biochemical response. The findings of this study demonstrate interspecific differences in fish response to parasite infections. High infection leads to an intensification of lipid peroxidation and a weakening of antioxidant protection in the muscles of mushroom goby but activation of the antioxidant enzyme system in the muscles of grass goby. The results show a greater resistance of grass goby to the infection when compared with mushroom goby.