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The occurrence of persistent organic pollutants (POPs) in the environment can affect organisms inhabiting aquatic systems, in particular shallow lakes that are vulnerable to environmental stressors. This study aimed to assess POPs accumulation and changes at histological and physiological levels in tissues of three fish species with different trophic habits. Gills, brain, muscle, liver and gonads of Odontesthes bonariensis, Oligosarcus jenynsii and Cyphocharax voga were collected from the shallow lake La Peregrina, located in an agricultural area from Argentina. In addition, contaminant levels in surface water (SW), suspended particulate matter (SPM) and bottom sediments (BS) were assessed. Histological lesions were evaluated in fish tissues and levels of vitellogenin (VTG) were assessed in plasma of male fish in order to correlate these alterations with the presence of POPs in the environment. Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were determined by GC-ECD. Biotic and abiotic samples showed the same POPs distribution pattern: OCPs>PCBs>PBDEs. Although tissue distribution of OCPs was species-specific, muscle showed the lowest levels in all species. The most abundant contaminants were endosulfans, suggesting their widespread use in the area. O. bonariensis showed the highest endosulfans levels in liver (184.2-219ngg(-1)wet w), which was associated with the high SPM levels considering this species is a filter feeder. The occurrence of PCBs and PBDEs shows the ubiquity of these pollutants in the area. Histological lesions in gills and liver of O. bonariensis and O. jenynsii, might be related with the high levels of endosulfans in these organs. The detection of VTG in males warns about a possible exposure to estrogenic compounds in the environment. In conclusion, the simultaneous exposure of fish to multiple environmental pollutants leads to different alterations, so measures should be taken in order to prevent their occurrence and toxic effects., (Copyright © 2016 Elsevier B.V. All rights reserved.)