Our body maintains homeostasis when we are exposed to external and internal stimuli. However, chronic stress changes the sympathetic and parasympathetic nervous systems as well as endocrine systems such as the hypothalamic-pituitary-adrenal (HPA) axis, which leads to a loss of homeostasis. This maladaptation triggers several kinds of disorders, like major depressive disorder (MDD), psychosomatic disease, and immune dysfunction. In addition, excess stress is known to affect the function of several brain areas, including the hypothalamic paraventricular nucleus (PVN), which plays a critical role in the adaptation to stress. In particular, corticotropin-releasing hormone (CRH) neurons are most strongly implicated in the stress response because the HPA axis is activated by facilitating CRH-containing neurons. Although the activation of CRH^PVN neurons may play a role in immune cell homeostasis, little is known about how the direct activation of CRH^PVN neurons may suppress immune cells. In this study, we investigated whether the specific activation of CRH^PVN neurons by DREADD systems could affect the peripheral immune system. As a result, the number of CD4⁺ T cells and NK cells was influenced by the activation of CRH^PVN neurons. Furthermore, there were correlations between the immune cell population and plasma cortisol levels. Taken together, these findings provide further evidence that the modulation of stress-associated PVN-CRH neurons may affect the peripheral immune system via the HPA axis.