Small mammals are routinely live-trapped and subsequently handled for a range of ecological and behavioural studies. Despite the techniques commonly employed being potentially stressful for the individual animals involved, it has hitherto been difficult to quantify the physiological impact. Here, we report on the first instance of using the Leukocyte Coping Capacity technique (LCC) in bank voles (Clethrionomys glareolus) and wood mice (Apodemus sylvaticus) to investigate the physiological impact of routine trapping and handling techniques. Twenty microlitres of blood were obtained from 40 animals, of which 25 were handled following standard protocols and 15 were not. We found that even a short period of acute stress is sufficient to trigger an immune response which was measurable using the LCC technique. These results further validate the use of the LCC technique for measuring the physiological impact of standard trapping and handling treatments on wild mammals.