The effects of wastewater from a mining and ore-dressing mill on fish in Lake Kostomukshskoe, which is used as a cesspool of circulating water and for storage of industrial wastes produced by the Kostomuksha mining and ore-dressing mill in northwest Russia, were studied. The lake is characterized by heavy mineralization, high pH, elevated levels of K(+), Li(+), SO4 (2-), NO(2-), Cl(-), Li, Mn, and Ni, and the presence of a fine-dispersed mechanical suspension. To assess the impact of contamination on fish and determine the mechanisms of their adaptation, we investigated the biochemical indices and histology of the liver of whitefish (Coregonus lavaretus L.) and pike (Esox lucius L.) inhabiting Lake Kostomukshskoe, downstream Lake Koyvas (64° 47' 30° 59'), and Lake Kamennoe, which is located in a nature preserve and has not been affected by anthropogenic activity (64° 28' 30° 13'). Changes were detected in the activity of metabolic enzymes (cytochrome c oxidase (COX), lactate dehydrogenase, and glucose-6-phosphate dehydrogenase) in the liver. Specifically, the COX activity in the liver of both fish species from the contaminated lake decreased, indicating a low level of aerobic metabolism. Lipid infiltration was the most visible and widespread change observed in the liver of both fish species; therefore, it can be considered a marker of such long-term contamination. Lesions in pike liver demonstrated a wider range of severity than in those of whitefish. In summary, metabolic enzyme activity and histomorphology of the liver of whitefish and pike differed among lakes in a species-specific manner. The changes in enzyme activity and histomorphological alterations in fish that were observed can be applied for evaluation of freshwater systems that may be subjected to mineral pollution.