Background: Atrial fibrillation (AF) has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. We compared serum markers of oxidation and associated inflammation in individuals with or without AF. Methods: Serum markers of oxidative stress and inflammation were compared in a cross-sectional, case-control design study of 40 male individuals, with or without persistent or permanent AF, who were matched for age, sex, diabetes, and smoking status, known confounding variables for the measurement of oxidative stress. We used derivatives of reactive oxidative metabolites (DROMs) and ratios of oxidized to reduced glutathione (Eh GSH) and cysteine (Eh CySH) to quantify oxidative stress. We also measured inflammatory markers, including high-sensitivity C-reactive protein, interleukins 1β and 6, and tumor necrosis factor α. Results: Univariate, conditional logistical regression analysis showed that oxidative stress but not inflammatory markers were statistically associated with AF (P <0.05). The increase in the odds ratios for AF for Eh GSH, Eh CySH, and DROMs were 6.1 (95% CI, 1.3-28.3; P = 0.02), 13.6 (95% CI, 2.5-74.1; P = 0.01), and 15.9 (95% CI, 1.7-153.9; P = 0.02), respectively. There was a stronger correlation between Eh GSH and Eh CySH (r = 0.66) than between Eh GSH and DROMs (r = 0.41). In multivariate analysis corrected for statins and other AF risk factors differing between the groups, the association of AF and oxidative stress remained significant. Conclusions: These data suggest that oxidative stress markers may have predictive value in AF management.