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Abstract Background: Recently, opioids have been related to trigger changes in cytokine release and tumor angiogenesis processes, influencing tumor growth, metastasis, and recurrence. Methods: This is a prospective randomized clinical study to test whether if exogenous opioids used in the anesthesia during cancer surgery can affect the systemic inflammatory and immunological patterns. Patients were randomly allocated to the OP (opioid-inclusive) or OF (opioid-free) anesthesia group. A total of 45 patients were selected, being carriers of prostate, stomach, pancreas, bile ducts, breast, colon, lung, uterus, kidneys, or retroperitoneum tumors. Plasma levels of IL-4, IL-12, IL-17A, and TNF-α, and their oxidative stress profile before and after surgery were evaluated in both groups. In vitro tests were performed by using healthy donor blood incubated with each isolated drug used in patients’ anesthesia for 1 hour, the same cytokines were measured in plasma. Results: There was a significant reduction in lipid peroxidation in both groups. Patients from OF group had a significant consumption of IL-12 in the perioperative period. The other cytokines evaluated did not vary. It was also observed a significant correlation between IL-12 and TNF-α levels in the OF-post group. Except for atracurium, all tested drugs led to a reduction in IL-12 levels. Conclusions: This study demonstrated that there is a reduction of IL-12 in the OF-post patients, suggesting acute consumption and that this seems to be a general mechanism of anesthetic drugs, as demonstrated in vitro. Also, these findings bring us to reflect if IL-12 changes may influence the disease progression and recurrence. Background Recently processes growth metastasis recurrence Methods patterns opioidinclusive opioid inclusive (opioid-inclusive opioidfree free (opioid-free 4 selected prostate stomach pancreas ducts breast colon lung uterus kidneys tumors IL4, IL4 IL 4, IL-4 IL12, IL12 12, 12 IL17A, IL17A ILA 17A, 17A IL-17A TNFα, TNFα TNF α, α groups hour plasma Results IL-1 period vary OFpost post atracurium Conclusions Also IL- IL1