Opioid receptor agonists modulate both innate and adaptive immune responses. In this study, we examined the impact of long-term chronic morphine administration on the circulating T cell population dynamics in rhesus macaques. We found that the numbers of circulating Treg cells, and the functional activity of Th17 cells, were significantly increased with chronic morphine exposure. Our results also show that T cell populations with surface markers characteristic of gut-homing (CD161 and CCR6) and HIV-1 susceptibility (CCR5 and β7 integrin) were increased. These results represent the first detailed report of the impact of chronic morphine administration on circulating T cell dynamics.