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Background: Total knee arthroplasty (TKA) is a successful and frequently performed procedure in orthopedic surgery. The diagnosis of peri-prosthetic joint infection following TKA remains challenging. The present study estimated the usefulness of knee skin temperature (measured by infrared thermography) and serum soluble intercellular adhesion molecule-1 (sICAM-1) in the diagnosis of post-operative knee peri-prosthetic infection., Methods: Patients were divided into three groups: 21 patients undergoing uncomplicated TKAs, seven with prosthesis infection, and three undergoing TKA revisions. The serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and sICAM-1 as well as the local knee skin temperature were measured pre-operatively and on Days 1 and 7 and at 1, 3, and 6 months post-operatively in Groups 1 and 3. The same parameters were measured in Group 2 at the time of prosthesis infection diagnosis., Results: In Group 1, the levels of IL-6, CRP, ESR, and knee skin temperature were significantly elevated post-operatively, but returned to baseline levels within 6 months. The sICAM-1 levels were not significantly different. The mean differential temperature (MDT) and levels of siCAM-1, IL-6, CRP, and ESR differed significantly between Groups 1 and 2. The MDT had returned to normal in Group 3 by 6 months post-operatively., Conclusions: Elevations in IL-6, CRP, ESR, and MDT in patients undergoing TKA could be a normal response to surgical trauma, but sustained elevations may be indicative of complications. The knee skin temperature and sICAM-1 may be used as indicators in the diagnosis of knee prosthesis infection following TKA.