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Reservoirs are important source of power generation, recreation, and water supply. Nevertheless, human activities have favored the bloom of toxic cyanobacteria in many reservoirs, which has resulted in environmental, social, and economic problems. This study aims to evaluate the water quality of a reservoir in South Brazil through the analysis of cyanobacteria and cyanotoxins PSTs (Paralytic Shellfish Toxins) and biomarkers of environmental contamination in fish. For this purpose, water samples and fish (Geophagus brasiliensis) (Perciformes: Cichlidae) were collected from September 2013 to May 2014. The fish G. brasiliensis were separated in two groups. The first one “site group” was euthanized after the sampling and their weight and length were measured. The blood, brain, muscle and liver were collected for chemical, biochemical and genetics biomarkers analysis. The second group “depuration group” was submitted to depuration experiment for 40 days in clean water. After that, the same procedures as for the first group were carried out. Cylindrospermopsis raciborskii was the dominant cyanobacteria found in the reservoir, and it showed a density above the recommended limit by Brazilian legislation of 20,000 cells/mL. Results showed that the fish accumulate PSTs in the Reservoir and these were not eliminated after 40 days. The biochemical and genotoxic biomarkers showed a significant difference between “site groups” and “depuration groups”, which suggests a recovery of the antioxidant system and a reduction of cellular damage after 40 days in clean water. In conjunction with results reported earlier by others, Alagados Reservoir, in South Brazil, appears to have a persistent contamination of cyanotoxins. Moreover, the mixture of contaminants which may be present in the water body can explain the seasonal differences in fish at the sampled points.Cyanobacterial blooms in Alagados Reservoir.Cyanobacteria densities above the recommended limit.Fish accumulated cyanotoxins.Cyanobacterial blooms can cause social, economic and environmental problems.