Background: The aim of this study is to investigate useful perioperative monitoring markers by comparing serial levels of serum procalcitonin (PCT), interleukin 6 (IL-6), and C-reactive protein (CRP) in routine surgical circumstances. Methods: In 285 surgeries of 277 patients, blood samples were obtained serially, at least three times per patient: within 48 h before surgery, 0-6 h after surgery (postOP1), >6-28 h after surgery (post-OP2), and/or later (postOP3). PCT, IL-6, and CRP were measured. Their demographic, operative, laboratory, and clinical data were collected retrospectively. Results: The systemic inflammatory response syndrome (SIRS) (n = 39) and sepsis (n = 11) groups showed higher post-operative values than the non-SIRS group (n = 233). Their maximum significant median levels were 8.96 vs. 0.21 mu g/L for post-OP2 PCT, 743.1 vs. 85.8 ng/L for post-OP1 IL-6, and 103.4 vs. 49.0 mg/L for post-OP2 CRP. Among non-SIRS patients, 12 patients developed undesirable post-operative events, including secondary surgery and death. The highest area under receiver operator characteristic curves was 0.92 at post-OP1 PCT (cut-off, 0.1 mu g/L; sensitivity, 91.7%; specificity, 78.7%), and the next highest was 0.84 at post-OP1 IL-6 (cut-off, 359 ng/L; sensitivity, 66.7%; specificity, 91.9%). All biomarkers were increased by non-specific surgical stimuli; however, post-OP1/post-OP2 PCT were <1.0 mu g/L (90th percentile) except major abdominal surgeries. Conclusions: Post-OP1 PCT measurement may be useful as a post-operative monitoring marker for the following reasons: pre-operative values less than the cut-off regardless of pre-operative state (age, malignancy, and American Society of Anesthesiologists class); minimal influence from surgical stimulus; and prediction of post-operative undesirable events.