The opioid system is involved in modulation of both innate and acquired immune responses, thus altering resistance to a variety of infectious agents. We sequenced and characterized carp opioid receptors (MOR, DOR, and KOR) and found their regulated expression in piscine leukocytes. Moreover, both in vivo and in vitro opioids affect activity of leukocytes and expression of inflammatory molecules, especially chemokines and chemokine receptors. Our data indicate an evolutionary conserved role for the opioid system in immune regulation.