Changes in the water quality of Lake Pskovskoe in 2000–2018 are considered. The water quality assessment employed a new ecotoxicological approach to comprehensive assessment of surface water pollution based on the risk of death from exposure to a wide range of concentrations (risk of combined exposure) in Daphnia. The new approach was applied to assess the among-year variation of the pollution of the lake with inorganic and organic harmful substances. A noticeable “negative trend” was detected in the risk posed by a combined action of pollutants and, hence in the water quality of Lake Pskovskoe, indicating a decrease in the concentration of pollutants from 2000 to 2018.