Aerobic organisms continually face exposure to reactive oxygen species (ROS) and many have evolved sophisticated antioxidant systems to effectively remove them. Any increase in ROS production or weakening in this defense system may ultimately lead to oxidative stress and cellular damage. We investigated whether long-term cold exposure, which is known to lead to an elevation in metabolic rate, increased the activities of the ROS-scavenging enzymes, catalase (CAT), selenium-dependent glutathione peroxidase (GPx), and total superoxide dismutase (Total-SOD) in liver, cardiac muscle, kidney, skeletal muscle ( vastus lateralis), and duodenum of short-tailed field voles ( Microtus agrestis), born and maintained at either 8 ± 3°C or 22 ± 3°C. CAT, GPx, and Total-SOD activities were determined at age 61 ± 1.9 days. An increase in CAT activity in voles maintained at 8 ± 3°C was observed in skeletal muscle (71%) and kidney (20%), with both CAT and GPx activities significantly elevated (by 40 and 43%, respectively) in cardiac muscle, when compared to voles at 22 ± 3°C. Total-SOD activity and protein content did not differ significantly between groups in any tissue. We suggest that the compensatory increases in CAT (skeletal muscle, cardiac muscle, kidney) and GPx (cardiac muscle), but not Total-SOD activities, resulting from long-term cold exposure may reflect the elevated metabolic rate, and possibly also increased ROS production, at this time.