Microcystins (MCYSTs) are toxins produced by cyanobacteria in aquatic environment and are of high potential risk to aquatic organisms. The physiological responses and pathobiological developments that they elicit in fish have been extensively studied, mainly through acute toxicity experiments. This study was designed to examine the seasonal fluctuation of biochemical markers of oxidative stress in different tissues of a natural population of Cyprinus carpio inhabiting a shallow Mediterranean lake, along with the respective MCYSTs concentrations in blood and tissues at environmentally relevant MCYSTs values. MCYSTs content was assessed in liver, kidney, intestine, brain and muscle along with the MCYSTs in lake water and scum applying ELISA technique. Catalase activity, GSH/GSSH relative concentrations and lipid peroxidation were used as biochemical markers. Our results suggest that common carp of Lake Pamvotis exposed to naturally fluctuating concentrations of MCYST in water and scum contained stably high MCYST concentrations in all tissues that might pose a threat to public health. Liver and kidney were the primary target organs. Tissue concentrations did not correlate with the response of any of the elements of the antioxidant defence system. Hepatic catalase, GSH content and TBARS in all tissues tested followed the fluctuations of major limnological parameters, i.e. water temperature and oxygen concentration, chlorophyll-a, MCYST in water and scum, suggesting that they should be cautiously used to monitor exposure to MCYSTS in natural freshwater ecosystems.