Lake Van fish is the only vertebrate species that lives in extreme condition (salinity of 2.2%, alkalinity of 151.2 meq/kg, and pH of 9.8) of largest soda lake of the world. This fish is an important source of protein for the people living in Van and surrounding provinces. . Cypermethrin (CYP) is used extensively against insects in agricultural, livestock, and domestic applications in Lake Van basin. CYP has toxic effects highly on non-target organisms as aquatic animals. The aim of this study was to evaluate the effect of commercial formulas of CYP (0.05 mu g/L) on Van Lake fish (Alburnus tarichi) for 24, 48, 72, 96 h under semi-static conditions using oxidative damage biomarkers. In this study, antioxidant defense system enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and lipid peroxidation (LPO) product malondialdehyde (MDA) levels were determined in the liver, kidney, gills, and brain tissues. According to the results of this study, the decrease in SOD (at 48, 72, and 96 h) and CAT and GPx (at 24, 48, 72, and 96 h) enzyme activities were significant with exposure to CYP (p < 0.05). In addition, the increase in MDA levels, which is the indicator of LPO, was found to be significant (p < 0.05). However, in the 24 h period exposed to CYP, a significant increase in SOD activity was determined in kidney and brain compared to the control group (p < 0.05). In conclusion, sublethal concentrate application of CYP is thought to cause oxidative stress and disrupt the oxidant, antioxidant balance of Lake Van fish.