BACKGROUND In recent years, emerging evidence has suggested that ulcerative colitis occurs as a consequence of an imbalance between oxidative stress and antioxidant capacity. The objective of this study was to investigate whether serum total bilirubin and serum uric acid levels were associated with ulcerative colitis. MATERIAL AND METHODS We conducted a retrospective case-control study which included 170 patients with ulcerative colitis and 200 healthy individuals. Concentrations of serum total bilirubin and serum uric acid were obtained from biochemical information and segregated into quartiles. Logistic regression analysis was adopted to explore the correlations between levels of the 2 biochemical markers and the risk of ulcerative colitis. RESULTS Compared with healthy controls, patients with ulcerative colitis exhibited lower levels of serum bilirubin (9.30 umol/L versus 12.49 umol/L respectively, P<0.001). Multivariate logistic regression showed that the lowest quartile of total serum bilirubin was independently associated with the occurrence of ulcerative colitis (OR=2.56, 95%CI: 1.54-4.25, P<0.001). Similarly, ulcerative colitis patients exhibited higher concentrations of serum uric acid (338 umol/L versus 300 umol/L respectively, P=0.041). Multivariate logistic regression showed that the highest quartile of serum uric acid was independently associated with ulcerative colitis risk (OR=1.20, 95%CI: 1.05-1.77, P=0.045). Furthermore, a negative association was observed between serum total bilirubin and serum uric acid in patients with ulcerative colitis. CONCLUSIONS Lower levels of serum total bilirubin and higher levels of serum uric acid are associated with ulcerative colitis patients compared to healthy controls.