Background: It is now recognized that the presence of a pre-op systemic inflammatory response (SIR) is associated with poor long term outcomes independent of tumour stage. However, although the post-op SIR has been associated with poorer short term outcomes, such as development of infective complications including anastomotic leak, and these complications have been implicated in poorer long term outcome, it is not clear whether the postoperative SIR is independently associated with long term outcome. Therefore, the aim of the present study was to determine whether post-op CRP concentrations were independently associated with long term outcome following potentially curative surgery for colorectal cancer. Methods: Data from consecutive patients (n=800) undergoing potentially curative resection of colorectal cancer from a single institution (March 1999 to May 2013) were studied. The relationship between post-op CRP on days 2, 3, and 4 (using standard thresholds for infective complications: day 2 CRP >190 mg/L, day 3 CRP >170 mg/L and day 4 CRP >145 mg/L) and cancer-specific survival (CSS) and overall survival (OS) was examined using Cox regression analysis. Results: The majority of patients were male (54%) and had node negative disease (61%). 26% received adjuvant therapy. Median follow up was 49 months with 169 cancer and 132 non-cancer deaths. On univariate survival analysis pre-op modified Glasgow Prognostic Score (mGPS) (HR 1.38, p=0.001), post-op day 2 CRP >190 mg/L (HR 1.47, p=0.012) and post-op day 3 CRP >170 mg/L (HR 1.46, p=0.018) were associated with CSS. On multivariate analysis both the mGPS (HR 1.20, p=0.080) and day 3 CRP >170 mg/L (HR 1.41, p=0.032) were independently associated with CSS and both the mGPS (HR 1.27, p=0.003) and day 3 CRP >170 mg/L (HR 1.32, p=0.027) were independently associated with OS. The post-op day 3 prognostic value was largely confined to the mGPS 0 group (HR 1.68, p=0.017 for CSS and HR 1.59, p=0.006for OS). Conclusions: Both the pre- and post-op SIR were independently associated with long term survival following surgery for colorectal cancer. The SIR is a useful unifying concept, linking surgery and outcomes in patients with cancer.