The thymus is a primary lymphoid organ where the primary T cell repertoire is generated. Thymus atrophy is induced by various conditions, including infectious diseases, glucocorticoid treatment, and poor breeding management. Cattle with thymus atrophy tend to exhibit weak calf syndrome, a condition in which approximately half of neonates die shortly after birth. Calves with thymus atrophy that survive the first month typically contract chronic inflammatory diseases. In this study, we analyzed the populations of the peripheral blood mononuclear cells and thymocytes in calves with thymus atrophy. In addition, we evaluated polarization of master gene and cytokine mRNA expression in peripheral blood CD4+ cells in the calves. The population of CD4+CD8+ cells in thymus of the calves with thymus atrophy was lower than that of control calves. IL10 mRNA expression in peripheral blood CD4+ cells of calves with thymus atrophy was significantly lower than that of control calves. TBX21 mRNA expression in peripheral CD4+ cells of thymus atrophy calves was tended to be higher than that of the control group. In addition, FOXP3 mRNA expression in peripheral CD4+ cells of the thymus atrophy calves was tended to be lower than that of the control calves. Thymus atrophy calves exhibited chronic inflammatory disease leading, in severe situations, to conditions such as pneumonia with caseous necrosis. These severe inflammatory responses likely are due to decreases in IL10 mRNA expression, impairing control of macrophages, one of the main cell fractions of natural immunity.