Introduction: Stressful condition induces physiological and behavioral changes in an organism to maintain the normal homeostasis. The response to stress is regarded as a positive adaptive process of an organism, which consist of a set of physiological and behavioral reactions to cope up with the challenging situations. In animals, stress study has shown to affect locomotor activities and behavioral changes. The present study was to determine the effect of cold water stress in different duration on neurobehavioral changes in swiss albino mice. Material and Methods: Male swiss albino mice weighing about 20 to 25gm were chosen for the study. The study consists of 4 groups (i) control, (ii) 1 day cold stress, (iii) 7 days cold stress and (iv) 14 days cold stress. The cold stress procedure was done by allowing the animal to swim in cold water at 14C for 5minutes every day. After the stress period, the neurobehavioral parameters were studied by using open field behavior and elevated plus maze. Results: There was a significant decrease in ambulation, rearing, grooming with a significant (P<0.001) increase in immobilization time of 1 day cold stress exposed group and 7th day cold stress exposed group in open field behavior model, whereas the 14th day stress group showed a significant decrease in ambulation only. In elevated plus maze, time spent in open arm was significantly decreased in 1st and 7th day stress group (P<0.001) and the number of entries in open arms and closed arms was significantly decreased in all stress exposed groups when compared with their respective control groups. Conclusion: Cold stress can affect hypothalamic- pituitary adrenal axis and thereby increase anxiety resulting in change in behavior and locomotor activity. When the stress period was prolonged to 7-14 days, there was a gradual recovery back to near normal. This type of behavior of the animals to prolonged stress could be attributed to habituation of the hypothalamo-pituitary adrenal axis.