Background: Tramadol hydrochloride is a centrally acting analgesic drug that has turned out to be a drug of growing interest due to its success in the management of pain in humans. By considering the twin mechanism of action of tramadol, as the activation of the opioid and of the monoaminergic systems, the potential immunological effects of this drug should be considered and be evaluated. Studies show that Tramadol induces an improvement of postoperative immune suppression and increases NK cell activity, lymphocyte proliferation, and IL-2 production which may be linked to its addictive potentiality. The present study aims to investigate the possible association between opioid use disorder (tramadol) and the serum level of interleukin-2 (IL-2). An observational cross sectional study conducted at the Outpatient Clinic and