Aim. The aim of this prospective comparative study was to evaluate the serum levels of different cytokines in patients underwent total knee replacement (TKR) and received allogeneic blood transfusion, post-operative auto-transfusion or not transfused. Material and Methods. This was a prospective non-randomized comparative study in 248 patients underwent TKR. Patient's demographic and clinical data including age, gender, body mass index (BMI), preoperative Hb value, complications were documented. The serum levels of IL-1b, IL-6, IL-8, IL-10, and TNF were measure pre-operatively, the 1st, 2nd, 3rd and 5th post-operative day. Patients were categorized in three groups; in Group 0 patients received no blood transfusion, in Group 1 patients received post-operative auto-transfusion and in Group 2 allogeneic blood transfusion was applied. Statistical analysis of the results was performed using repeated measures ANOVA. Results. Significant changes were observed in cytokines levels in Groups 1 and 2. In Group 1 (auto-transfusion) the levels of all cytokines significantly increased the 1st postoperative day, remaining above the pre-operative levels even the 5th post-operative day. In Group 2 (allogenic transfusion), although the levels of IL-6, IL-8 and IL-10 were also significantly increased the 1st postoperative day, they gradually returned to the per-operative levels by the 5th post-operative day. In Group 0 (no transfusion) the only significant increase was observed in IL-6 between pre-operative and 1st and 3rd day values. Furthermore, the area under the curve (AUC) of IL-1b, IL-6, IL-8 and IL-10 levels in Group 1 and AUC of IL-6, IL-8 and IL-10 levels in Group 2, were significantly higher compared to Group 0. There was no significant difference in post-operative patient's complications. Conclusion. According to the results of this study significant elevation of cytokine values were observed during the first five post-operative days in patients received blood transfusion after TKR. These changes were more pronounced in the auto-transfusion group