Background While the current literature suggests an association with frailty and clinical outcomes in patients undergoing surgery for colorectal cancer (CRC), the basis of this relationship is unclear. Aim Examine the relationship between frailty, malnutrition, body composition, systemic inflammation and short-term clinical outcomes in patients undergoing surgery for colorectal cancer. Methods Consecutive patients who underwent potentially curative resection for colorectal cancer, between April 2008 and April 2018, were identified from a prospectively maintained database. Frailty was defined using the modified five-item frailty index (mFI-5). Body composition measures included CT-derived skeletal muscle index (SMI) and density (SMD). Systemic inflammatory status was determined using Systemic Inflammatory Grade (SIG). Outcomes of interest were the incidence of post-operative complications and thirty-day mortality. Associations between categorical variables were examined using χ2 test and binary logistics regression analysis. Results 1002 patients met the inclusion criteria. 28% (n = 221) scored 2 or more on the mFI-5. 39% (n = 388) of patients had a post-operative complication (Clavien-Dindo I-IV) and 1% (n = 11) died within thirty days of surgery. On univariate analysis, mFI-5 frailty score, was significantly associated with advanced age (p < 0.001), colonic tumours (p < 0.001), reduced use of neo-adjuvant chemotherapy (p < 0.05), higher BMI (p < 0.05), low SMD (p < 0.001), elevated NLR (p < 0.05), elevated mGPS (p < 0.05), elevated SIG (p < 0.05), incidence of post-operative complications (p < 0.001) and thirty-day mortality (p < 0.05). On multivariate analysis, male sex (p < 0.05), elevated SIG (p < 0.05) and mFI-5 score (p < 0.01) remained significantly associated with the incidence of post-operative complications. mFI-5 frailty was found to remain significantly associated with the incidence post-operative complications in patients who were SIG 0 (p < 0.05). Conclusion mFI-5 frailty score was found to be significantly associated with age, systemic inflammation and post-operative outcomes in patients undergoing potentially curative resections for CRC. Incorporation of an assessment of systemic inflammatory status in future frailty screening tools may improve their prognostic value.