Abstract Background Determining disease activity in ulcerative colitis (UC) patients is important in order to reduce surgery rate and mortality. Colonoscopy has the disadvantage of being invasive, time consuming and expensive. Several laboratory markers have been proposed in order to evaluate UC disease activity. Methods The aim is to investigate the utility of neutrophil-lymphocyte ratio (NLR), neutrophil-monocyte ratio (NMR), and lymphocyte-monocyte ratio (LMR) in differentiating active UC from UC in remission. This is a prospective study carried out at a hospital center in Albania, from 2019–2020. Demographic and endoscopic data along with complete blood counts were collected for each UC patient. Based on Mayo score system, patients were classified as active UC (total Mayo score >2 points) and UC in remission (total Mayo score ≤ 2 points). Pearson correlation coefficient was used to analyze associations between parameters. The sensitivity, specificity, and cut-off values were assessed using a receiver operating characteristic curve analysis. Results 65 UC patients, with a mean age of 45.05 ± 15.5 (16–85) years, of whom 52.3% were females and 47.7% males, were enrolled in this study. 21.4% were in remission and 63.4% were classified as active UC disease. We found a positive correlation between NLR, NMR and disease activity [(r=0.295, p=0.002); (r=0.241, p=0.011) respectively]. NLR and NMR were also significantly higher in active disease group compared to UC in remission (p=0.016 and p=0.03 respectively). ROC analyses revealed that NLR (AUC=0.664, 95% CI, 0.557–0.772) and NMR (AUC=0.644, 95% CI, 0.531–0.756) are satisfactory in differentiating active UC from UC remission patients. A NLR cutoff value of 2.1 had a sensitivity of 60% and specificity of 61% for active UC, while a NMR cutoff value of 12.2 had a sensitivity of 63% and a specificity of 61% for active UC. We didn’t found any correlation between LMR and disease activity Conclusion This study shows that NLR and NMR are significantly associated with active UC disease. Given the fact that complete blood count is widely available and inexpensive, NLR and NMR may play a role in differentiating active UC from UC in remission.