Background: Ulcerative colitis (UC) is a long-standing inflammatory disease with remission and exacerbation courses. Early detection of relapses, flares, disease activity changes, and treatment responses is key to optimizing patient management. The evidence about the usefulness of low-cost blood test inflammatory markers concerning UC disease activity is still limited. This study aimed to evaluate the diagnostic accuracy of low-cost serum inflammatory markers in monitoring UC activity. Methods: This cross-sectional study was conducted in the inflammatory bowel disease (IBD) clinic, Zagazig University Hospital, Egypt. Fecal calprotectin and low-cost serum inflammatory markers including C-reactive protein (CRP), C-reactive protein-albumin ratio (CAR), lymphocyte-monocyte ratio (LMR), mean platelets volume-lymphocyte ratio (MLR), mean platelets volume-platelets ratio (MPR), neutrophil-lymphocyte ratio (NLR), platelets-lymphocyte ratio (PLR), red cell distribution width-platelet ratio (RPR), and systemic immune-inflammation index (SII) were measured. Results: The area under the curve (AUC) of CRP, CAR, Fecal calprotectin, LMR, SII, and MPR in the diagnosis of severe UC were 0.85, 0.85, 0.84, 0.81, 0.83, and 0.80 respectively. CRP, CAR, Fecal calprotectin, NLR, LMR, SII, Albumin, MPR, and RPR were independent predictors for Mayo score grade 3. Conclusion: low-cost serum inflammatory markers such as CRP, CAR, LMR, SII, and MPR showed diagnostic accuracy in monitoring severe UC activity.