Background: Surgical site infections (SSI) are a common surgery complication which early diagnosis is important to initiate an adequate therapy promptly. Objective: To explore the possibility of using serum Interleukin-6 (IL-6) in patients who had major surgery as a biomarker to predict SSI. Patients and Methods: From October to December 2011, 50 patients who underwent major surgery in Sardjito General Hospital Department of Surgery, Yogyakarta were followed up for their IL-6 serum on the third day following the surgery. The patients were also assessed whether they contracted SSI or not. Results: SSI was present in sixteen out of 45 patients (35.6%). The serum IL-6 level was higher in the group which SSI present where 84.5% of the sample was higher than 10 pg/ml. The Chi-square test showed SSI is related to abnormal IL-6 level (OR 4.941, p<0.05). Conclusion: Post-operative IL-6 higher than normal serum level was associated with SSI. The result indicates that IL-6 serum level may be a useful predictor of the occurrence of SSI in patients who underwent major surgery.