Background: Most Crohn's Disease (CD) patients will require surgical intervention over their lifetime, with considerably high rates of post‐operative complications. Risk stratification with reliable prognostic tools may facilitate clinical decision making in these patients. Blood cell interaction based inflammatory markers have proven useful in predicting patient outcomes in oncological and benign diseases. The aim of this study was to investigate their prognostic value in CD patients undergoing surgery.Methods: A retrospective single institution study of CD patients who underwent surgery between the years 2008 and 2019 was conducted. Data were collected from medical records and analysed for association of Platelet‐to‐Lymphocyte Ratio (PLR), Neutrophil‐to‐Lymphocyte Ratio (NLR), Lymphocyte‐to‐Monocyte Ratio (LMR) and the modified Systemic Inflammatory Score (mSIS) with post‐operative outcomes.Results: A total of 81 patients were included in the analysis. Half were females; mean age was 36 ± 15.54 years. Fifty seven percent (n = 46) were operated in expedited settings, with 23.5% developing post‐operative complications. In elective patients, higher pre‐operative NLR (P = 0.029) and PLR (P = 0.034) were associated with major post‐operative complications, higher NLR (P = 0.029) and PLR (P = 0.034) were associated with re‐operation and higher PLR correlated with Clavien‐Dindo score (P = 0.032). In patients operated in expedited operations, higher pre‐operative NLR (P = 0.021) and lower pre‐operative LMR (P = 0.018) were associated with thromboembolic events and higher mSIS was associated with major post‐operative complications (P = 0.032).Conclusions: Blood cell interaction based inflammatory markers confer an association with post‐operative complications in CD patients undergoing surgery. These indices may facilitate patient selection and optimization when considering the risks and benefits of surgical interventions.