The object of our study of the functional activity of the body's immune reactions over a long period (2021–2024) was Pelophylax ridibundus in the reservoir of an urbanized territory (Silikatnoye Lake, Nizhny Novgorod) infected with Hepatozoon spp. A hydrochemical analysis of the habitat of P. ridibundus was done. Intraerythrocyte parasites were accounted for with the calculation of the extent and intensity of invasion and abundance of hemoparasites. The functional activity of the humoral immunity of individuals was determined by the level of large and small immune complexes, with calculation of the ratio of large to small immune complexes. The infection rate of frogs remained relatively high during the four-year monitoring period. During this four-year monitoring, the total content of large immune complexes in uninfected individuals did not change; whilst in infected individuals, this indicator was significantly higher when living in a more polluted environment (water quality class 4). An increase in the functional activity of the immune system of infected P. ridibundus was revealed in conditions of higher chemical pollution of the environment. The ratio of large to small immune complexes in infected frogs (water quality class 4) was higher than in individuals living in a less polluted environment (water quality class 3). A decrease in the level of large immune complexes and the ratio of large to small immune complexes in infected individuals was found with an improvement of their habitat. A dependence of the decrease in the ratio of large to small immune complexes of P. ridibundus on the content of copper and iron ions in the water body has been revealed. Differences in the functional activity of immune responses of uninfected and infected individuals are shown, determined by the conditions of chemical pollution of the environment.