Background: This study was designed to assess the efficiency of combined bilateral superficial and deep cervical plexus blocks with general anesthesia in patients undergoing total laryngectomy with respect to the anesthetic requirements, immune response and postoperative pain. Method: The patients (40) were allocated randomly to one of two groups: General Anesthesia Group (GA) (n=20) and Combined Group (regional and general anesthesia) (n=20). After assessment of the airway, the method of induction of anesthesia was chosen. The maintenance of anesthesia in both groups was achieved by sevoflurane with fresh gas flow 5 L/min. In Combined Group, before giving general anesthesia, the patients received combined bilateral superficial and deep cervical plexus block. The hemodynamic goals were to maintain the mean arterial pressure (MAP) at 60-65 mm Hg by adjusting the sevoflurane concentration and the use of esmolol. The consumption of sevoflurane and the Frequency of use of esmolol were evaluated in both groups. Intraoperative blood loss was assessed. In the ICU, VAS pain scores and total morphine consumption were assessed every 30 minutes in the ICU for 3 hours. Venous blood samples were obtained of measurement of serum IL2 and SIL-2R levels before induction of anesthesia, at the end of surgery, and in the mornings of 1st and 5th postoperative days. In addition, serum samples also were collected from 40 healthy volunteers for comparison. Results: The number of patients requiring supplemental fentanyl, and the mean end tidal sevoflurane concentration were significantly increased in GA Group. The mean heart rates values and mean arterial pressure were significantly reduced in the combined group. All patients in GA Group required supplemental esmolol to achieve the target MAP, in contrast only 5 patients in the Combined Group required supplemental esmolol (p<0.001). A reduction in blood loss was observed in the Combined Group during the surgical procedure (p<0.001). In the ICU, the total morphine administration (PCA and additional doses) was significantly less in the Combined Group than in the GA Group (7.8 ± 2.7 vs. 12.2 ± 1.9, p<0.05). The mean VAS for pain was significantly less in the combined group. Conclusion Cancer larynx is associated with a state of immunosuppression. The combined bilateral superficial and deep cervical block with general anesthesia is an effective technique to reduce anesthetic and analgesic requirements during and after total laryngectomy and has less depressant effect on the immune response.