There is increasing evidence that stress produces changes in various immune processes. Some of these changes may be due to neurochemical and hormonal alterations including thyroid hormones levels. This work was carried out to study the impact of chronic mild stress (CMS) exposure on proliferative responses and its correlation with serum thyroid hormone levels. In addition, the influence of serum corticosterone levels on these responses was also studied. For this purpose, mice were submitted from1 to 6 weeks to a CMS model. After undergoing the stress schedule for 4 weeks, an alteration in the proliferative response was observed. Lymphocytes from exposed animals showed a decrease in T-cell response to concanavalin-A (Con A) and phytohemagglutinin (PHA) and an increase in B-cell proliferation to lipopolysaccharides (LPS). In parallel, a reduction in T3 and T4 serum levels was observed. On the contrary, serum corticosterone levels increased in animals exposed to CMS for 1 or 2 weeks and then return to normal values. Lowering serum thyroid hormone levels by propylthiouracil (PTU) treatment negatively modulates T-cell response without affecting B-cell response. On the other hand, the substitutive T4 treatment in stressed animals improved significantly the proliferative T-cell response. Non-significative changes in CD4/CD8 ratio were observed neither in stressed, PTU- or T4-treated animals. Taken together, our results suggest an impact of chronic stress on thyroid function that in turn alters T-cell response. These findings may help to elucidate the physiological mechanisms through which stress plays a roll in the etiology of many diseases.