Effects of cold stress on immune function and energy demand were experimentally investigated in the grey-sided vole. Laboratory-born and wild voles were divided into two groups: one maintained at 5°C (low temperature) and the control at 23°C (room temperature). The voles exposed to low temperature showed a weaker immune response to the challenge antigen than the control voles. Food intake of the voles under low temperature increased in comparison with that of the control, and fat reserves reduced in the voles under low temperature. Kidney, heart and small intestine of the voles were hypertrophied by approximately 10–20% compared with the controls. These results can be interpreted as a trade-off between thermoregulation and immunity. These physiological reactions caused by low temperature may cause higher mortality of grey-sided voles during winter (the non-breeding season) in the field.