In this study, the association between heavy metals in water and cyprinids sampled from the Yeilrmak River stretch, which is frequently exposed to pollutant sources (a sugar production factory (Turhal) and solid wastes dump area (Talciftlik) was explored, and the oxidative effects of heavy metals on cyprinids were evaluated through analyzing some liver enzymes, namely, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and cortisol. The heavy metal concentrations of both fish and water, collected from three different locations along the river during the summer of 2011 and winter of 2010 (Turhal, Talciftlik, and Gumenek), were determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES). The water and fish liver heavy metal concentrations exhibited increasing trends from upstream (Gumenek) to downstream (Turhal). The water and liver samples collected during the summer had higher heavy metal concentrations than those obtained during the winter. The mean heavy metal concentrations increased from Gumenek to Turhal. The liver heavy metal concentrations were higher than those in the water and exhibited almost the same increasing trend from Gumenek to Turhal. Positive relationships between liver and water heavy metal concentrations, especially for cadmium (R-2 = 0.91) and lead (R-2 = 0.98), were obtained. Among the liver enzymes, only MDA followed the same increasing trend from Gumenek to Turhal as was obtained for heavy metals. On the other hand, CAT and SOD had a contrary spatial pattern of change to those of heavy metals and MDA. Although the values of heavy metals and MDA in Talciftlik were between the two other locations, fish inhabiting this locality had significantly higher values of cortisol, which is an indication of the other stress-causing factors for fish.