Ambient temperature is an important factor influencing many physiological processes, including antioxidant defense and immunity. In the present study, we tested the hypothesis that antioxidant defense and immunity are suppressed by high and low temperature treatment in Brandt’s voles (Lasiopodomys brandtii). Thirty male voles were randomly assigned into different temperature groups (4, 23, and 32 °C, n=10 for each group), with the treatment course lasting for 27 d. Results showed that low temperature increased gross energy intake (GEI) and liver, heart, and kidney mass, but decreased body fat mass and dry carcass mass. With the decline in temperature, hydrogen peroxide (H2O2) concentration, which is indicative of reactive oxygen species (ROS) levels, increased in the liver, decreased in the heart, and was unchanged in the kidney, testis, and small intestine. Lipid peroxidation indicated by malonaldehyde (MDA) content in the liver, heart, kidney, testis, and small intestine did not differ among groups, implying that high and low temperature did not cause oxidative damage. Similarly, superoxide dismutase (SOD) and catalase (CAT) activities and total antioxidant capacity (T-AOC) in the five tissues did not respond to low or high temperature, except for elevation of CAT activity in the testis upon cold exposure. Bacteria killing capacity, which is indicative of innate immunity, was nearly suppressed in the 4 °C group in contrast to the 23 °C group, whereas spleen mass and white blood cells were unaffected by temperature treatment. The levels of testosterone, but not corticosterone, were influenced by temperature treatment, though neither were correlated with innate immunity, H2O2 and MDA levels, or SOD, CAT, and T-AOC activity in any detected tissues. Overall, these results showed that temperature had different influences on oxidative stress, antioxidant enzymes, and immunity, which depended on the tissues and parameters tested. Up-regulation or maintenance of antioxidant defense might be an important mechanism for voles to survive highly variable environmental temperatures.