Background: An oxidative balance score (OBS) that combines pro-And antioxidant exposures was previously reported to be associated with incident sporadic colorectal adenoma. We extend the previous analyses by assessing associations of the OBS and colorectal adenoma with circulating biomarkers of oxidative stress [F2-isoprostanes (FIP) and fluorescent oxidation products (FOP)], and inflammation [C-reactive protein (CRP)]. Methods: Using pooled data from two previously conducted colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 365), the OBS was constructed and divided into three approximately equal intervals, with the lowest interval used as the reference. Biomarker levels were dichotomized as "high" versus "low" based on the median values among controls. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: For the OBS-Adenoma association, the ORs (95% CIs) for the middle and highest (relative to the lowest) score intervals were 0.81 (0.46-1.43) and 0.39 (0.17-0.89), respectively. The corresponding OBS category-specific ORs (95% CIs) were 0.50 (0.25-1.01) and 0.25 (0.10-0.65) for FIP, 2.01 (1.13-3.75) and 3.48 (1.51-8.02) for FOP, and 0.57 (0.31-1.04) and 0.21 (0.09-0.49) for CRP. The ORs (95% CIs) reflecting associations of adenoma with high levels of FIP, FOP, and CRP were 1.89 (1.08-3.30), 1.82 (1.11-2.99), and 1.45 (0.88-2.40), respectively. Conclusions: As hypothesized, the OBS was inversely associated with colorectal adenoma and circulating FIP and CRP levels. The reason for the unexpected direct OBS-FOP association is unknown. Impact: These data support the use of combined measures of pro-And antioxidant exposures in studies of colorectal neoplasia. © 2014 American Association for Cancer Research.