Aim To compare the effect of adjunctive lidocaine-based scalp block and laryngotracheal local anesthesia vs general anesthesia only on pro-inflammatory cytokine concentrations in patients with non-ruptured brain aneurysms undergoing elective open surgery. Methods This parallel, randomized, controlled, open-label trial was conducted at Clinical Hospital Center Zagreb between March 2019 and March 2020. At the beginning of anesthesia, lidocaine group received 40 mg of 2% lidocaine for laryngotracheal topical anesthesia and 4 mg/kg for the scalp block. Control group underwent general anesthesia only. Plasma concentrations of IL-6, TNF-alpha, and IL-1beta were measured before anesthesia (S0); at the incision (SI); at the end of surgery (S2); 24 hours postoperatively (S3). Cerebrospinal fluid (CSF) cytokine concentrations were measured at the incision (L1) and the end of surgery (L2). Results Forty patients (each group, 20) were randomized; 37 were left in the final analysis. IL-6 plasma concentrations increased significantly compared with baseline at S3 in lidocaine group, and at S2 and S3 in control group. In both groups, changes in TNF-alpha and IL-1beta were not significant. CSF cytokine concentrations in lidocaine group did not change significantly; in control group IL-6 and IL-1beta were significantly higher at L2 than at L1. CSF IL-6 in control group significantly increased at L2, but TNF-alpha and IL-1beta did not. No differences in clinical outcome and complication rates were observed. Conclusion Adjunctive lidocaine-based scalp block and laryngotracheal local anesthesia might attenuate CSF IL-6 concentration increase in patients with brain aneurysm. Trial registration Clinical Trials NCT03823482