Endomorphins are endogenous high-affinity selective agonists of the μ-receptor, which is expressed on the cells of the immune system, due to which endomorphins can have an immunomodulatory effect. The aim of this study was to estimate the effect of endomorphin-1 and endomorphin-2 on the functional activity of monocytes and neutrophils in peripheral blood in vitro. It was found that endomorphin-1 reduces spontaneous production of reactive oxygen species by leukocytes and the intensity of respiratory burst in stimulated neutrophil cultures. Endomorphin-2 inhibited spontaneous production of oxygen radicals by the leukocyte fraction of peripheral blood, stimulated spontaneous production of reactive oxygen species by the neutrophil fraction, but suppressed their induced production. Endomorphin-1 increased the rate of monocyte phagocytosis, enhanced spontaneous IL-1β production, and inhibited stimulated IL-10 production by mononuclear cells. Endomorphine-2 also enhanced spontaneous IL-1β production and reduced stimulated IL-10 production by mononuclear cells, stimulated the absorption activity of both neutrophils and monocytes. Thus, endomorphins are important modulators of the functional activity of innate immunity effector cells.