Uncoupling proteins (UCPs) are located in the inner membrane of mitochondria. The first discovered uncoupling protein 1 (UCP1) is well known for its potential to uncouple adenosine 5’ triphosphate (ATP) synthesis from energetic substrate oxidation, resulting in heat production. Its partially homologue uncoupling protein 2 (UCP2) is found in several tissues and has been reported to reduce reactive oxygen species (ROS) production and seems implicated in the regulation of energetic substrates. According to our knowledge, the expression of Ucp2 in the hypothalamic-pituitary-adrenal (HPA) axis has not been described yet, neither its implication in stress response. Our study presents i) the distribution of Ucp2 mRNA in the HPA axis, ii) the effect of stress on Ucp2 expression in the brain and HPA axis and iii) the stress response of Ucp2 deficient mice (Ucp2 KO) to evaluate whether or not the absence of Ucp2 affects the stress response in mice. Although we do not detect any difference between Ucp2 KO mice and wild type (WT) mice following a stress, we have shown that Ucp2 is expressed in abundance in the HPA axis. Many brain regions also present an increase in Ucp2 expression after a stress.