Abstract: Objective To investigate the effects of threedifferent anesthesia methods on perioperative stress in patients undergoing unilateral total knee arthroplasty (UTKA). Methods Medical records of patients admitted for UTKA in our hospital from January todecember in 2014 were analyzed. Patients weredivided into three groups: general anesthesia (GA) group (n=204), nerve block (NB) group (n=44) and epidural anesthesia (EA) group (n=49), and their gender, age, height, weight and theduration of operation in three groups were recorded. The level of serum C reactive protein (CRP) and interleukin-6 (IL-6) was measured at preoperative (T0) and 1, 3 and 5days after operation (T1, T2, T3). At the same time, the occurrence of fever, wound infection, joint effusion anddeep venous thrombosis were recorded. Results There was no significantdifference in gender composition, age, height, weight, and operation time between three groups (P> 0.05). From the time point of view, CRP reached peak at the thirdday after surgery and IL-6 began to rise at the firstday after surgery of patients in three groups with significantdifferences when compared with before treatment (P< 0.05). Compared with GA group, the serum CRP and IL-6 in NB group was significantly higher (6.3±2.0) mg/L vs (5.8±3.4) mg/ L; (52.7±31.0) ng/L vs (40.6±38.9) ng/L, P< 0.05. There was no significantdifference in postoperative complications between three groups (P> 0.05). Conclusion The inflammatory factors increase in all patients with UTKA on the firstday after surgery. Compared with simple EA and NB, general anesthesia can obviously reduce the stress reaction of patients, which suggests that it is a suitable method for patients with UTKA.