The aim of the present study was to determine the level of selected toxicants in water, their bioaccumulation and effects on antioxidant enzymes i.e. superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) in vital organs (gills, liver and kidney) of fish, Cirrhina mrigala. The 3 different representative water samples and 60 fish samples (20 fish from each site) were collected from three sites i.e. fish-farm, hatchery and Indus River of Punjab, Pakistan. The results showed differences in physico-chemical parameters of water samples collected from all the sites. The concentrations of Zinc (Zn), copper (Cu) and nickel (Ni) were higher in river water as compared to farm and hatchery. Different organs of fish collected from different sites showed variations in their metal concentration. In Indus River fish, the concentrations of metals were highest in liver followed by kidney and gills. The Indus River fish also exhibited highest SOD activity in all the organs as compared to farm and hatchery fish. The activity of CAT enzyme was higher in kidneys and gills of farm fish compared to the liver of hatchery fish. The maximum POD activity was recorded in liver, kidney and gills of hatchery fish. This study reveals that fish could acquire higher uptake of metals due to excessive pollution of heavy metals and other toxic elements in river water. In response to metals toxicity, the antioxidant system can be useful as an early warning tool in natural monitoring studies.