Endomorphins – endogenous tetrapeptides with the highest affinity for the µ-opioid receptor. Currently, two tetrapeptides that differ in one amino acid residue have been isolated and characterized. The structure of endomorphins differs from the structure of members of three main families of opioid peptides: endorphins, enkephalins, and dynorphins, which contain the same N-terminal sequence. In the central nervous system, endomorphins are distributed everywhere, where they are primarily responsible for antinociception. Distribution of endomorphins in the immune system, similar to that of other opioid peptides, has allowed to suggest their active participation in the processes of immune regulation. This review summarizes modern views on the structure of endomorphins, their localization, possible intracellular mechanisms of signal transmission and their effects on the processes of activation, proliferation and differentiation of cells of innate and adaptive immunity. Endomorphins actively modulate the functions of the cells of the immune system. Peptides predominantly suppress adaptive immunity reactions. There effects on the functions of innate immunity cells (granulocytes, macrophages, monocytes, dendritic cells) depending on the conditions and can have either an inhibitory or stimulating orientation. Thus, endomorphins can be promising compounds that can effectively regulate both nociceptive signals and processes in the immune system.