It is well known that chronic stress can have serious health consequences, leading to depression, anxiety, hypertension, obesity, diabetes, and so on. Additionally, the stress-induced impact results in a decrease in immune system functions, rendering the body more susceptible to infections and other illnesses. In addition to regulating sleep, melatonin possesses pleiotropic properties: it inhibits oxidative stress, exhibits anti-aging effects, and demonstrates documented anti-cancer activity. Melatonin is an effective antioxidant that stabilizes mitochondria. It remains incompletely understood how melatonin affects immune defence under conditions of chronic stress.This study aimed to determine the influence of melatonin on certain indicators of the immune system under conditions of stress exposure. Three groups of laboratory mice of the BALB/c strain were formed. The first group was kept under a 12-hour light-dark cycle. The second and third groups were subjected to chronic stress through constant illumination. The third group of animals additionally received exogenous melatonin in their drinking water. On the fifth, fifteenth, and thirtieth days of the experiment, indicators of leukocyte levels, phagocytic activity using the latex particle uptake method, and the Th1-dependent immune response were determined by the intensity of delayed-type hypersensitivity reactions.Comparison of the indicators revealed that in the second group on the 5th day of the experiment, there was an increase in the total number of leukocytes, an elevation in the level of neutrophils, and a decrease in the level of monocytes. Animals receiving melatonin demonstrated similar results. At the end of the experiment, in the group receiving melatonin, the level of neutrophils decreased against an elevated level of lymphocytes and monocytes.At the end of the experiment, the group subjected to chronic stress demonstrated a decrease in the number of colony-forming units. However, in the melatonin-treated group, the opposite was observedan increase occurred. A similar trend was observed in the determination of hypersensitivity activity. In the melatonin-treated group, hypersensitivity indicators were higher compared to the group not receiving melatonin. Phagocytic activity in the third group was already higher on the fifth day of the experiment.The results of the study indicate that the administration of melatonin has a positive impact on certain indicators of the immune system under conditions of chronic stress. Specifically, phagocytic activity increased, the level of lymphocytes was elevated, antibody production intensified, and delayed hypersensitivity reaction was enhanced.