Background: Colorectal cancer is the second commonest cause of cancer death in Europe and North America with rectal cancer making up a third of this disease burden. Markers of the systemic inflammatory response (SIR) have been shown to be prognostic in cancer. These include ratio of different white blood cells/acute phase proteins such as NLR (neutrophil/lymphocytes), PLR (platelets/lymphocytes), LMR (lymphocytes/monocytes) and CAR (CRP/albumin) and cumulative prognostic scores such as NPS (Neutrophil Platelet Score)/mGPS (modified Glasgow Prognostic Score). The aim of the present study was to compare the prognostic value of SIR markers in patients undergoing surgery for rectal cancer. Methods: A prospectively maintained database of all patients undergoing elective curative rectal resection in our institution was examined. The SIR was measured by the ratios and scores NLR, PLR, LMR, CAR, NPS and mGPS using standard thresholds NLR (>5), PLR (>150), LMR (<2.4), CAR (>0.24), NPS (0, 1, 2) and mGPS (0, 1, 2). Statistical analysis was carried out in SPSS using ROC curve and Cox regression analysis for both cancer specific survival (CSS) and overall survival (OS). Results: Of the 393 patients included in the study, 237 (60%) were male, 91 (25.6%) had neoadjuvant therapy, 341 (87%) had open surgery, 285 (72.5%) had T3/4 disease and 155 (39.4%) and node positive disease. On ROC curve analysis, validated ratios and scores such as NLR (AUC: 0.534 95%CI 0.469-0.600), PLR (AUC: 0.526 95%CI 0.444-0.607), LMR (AUC: 0.574 95%CI 0.472-0.676), CAR (AUC: 0.551 95%CI 0.487-0.615), NPS (AUC: 0.578 95%CI 0.513-0.643) and mGPS (AUC: 0.571 95%CI 0.513-0.629) showed considerable similarities. On multivariate categorical analysis with TNM stage there was a significant relationship between CSS and NPS (HR: 2.09 95%CI 1.14-3.82, p=0.017), CAR > 0.22 (HR: 1.64 95%CI 1.09-2.47, p=0.018) and mGPS (HR: 3.06 95%CI 1.71-5.47, p < 0.001). Conclusions: The SIR as measured by a number of scores/ratios had prognostic value in patients with rectal cancer. Only the NPS and mGPS had prognostic value independent of TNM stage. These scores may be useful in stratifying treatment in patients with rectal cancer.