Introduction: Complications following oesophagogastric surgery have significant implications for patient recovery. Objective: identify cost-effective biomarkers which can predict morbidity. Methods: Analysis of all upper gastrointestinal resections in Galway University Hospital from 2014 to 2018 was performed. The ability of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and CRP-lymphocyte ratio (CLR) to predict morbidity, including anastomotic leak (AL), was assessed and compared. Results: Seventy-one oesophagectomies and 77 gastrectomies were performed. There were 2 (1%) 30-day mortalities and 83 (56%) morbidities of which 30 (20%) were of Clavien-Dindo grade 3 or higher. The rate of major morbidity within the oesophagectomy cohort was 27% and was 14% in the gastrectomy cohort. There were 11 (7%) ALs, 7 in the oesophagectomy cohort, and 4 in the gastrectomy cohort. From post-operative day (POD) 2 onwards, CRP could predict AL (POD2 AUC = 0.705, p = 0.025; POD3 AUC = 0.757, p = 0.005, POD4 AUC = 0.811, p = 0.001; and POD5 AUC = 0.824, p = 0.001). CLR predicted AL on POD2 onwards (POD2 AUC = 0.722, p = 0.005; POD3 AUC = 0.736, p = 0.01; POD4 AUC = 0.775, p = 0.003; and POD5 AUC = 0.817, p = 0.001). CRP level of 218 mg/dL and CLR level of 301 at POD 2 generated negative predictive values of 97 and 98%, respectively, for AL. Post-operative NLR did not display sufficient discriminatory ability for the outcomes. Conclusion: CRP and CLR are reliable negative predictors of major morbidity, including AL, after oesophagogastric resection. Their use can inform patient intervention and recovery.