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Frailty, a clinical syndrome characterized by multisystem dysregulation, has been associated with high levels of oxidative stress. We investigated the association between serum total antioxidant capacity (TAC) and frailty in older men. This cross-sectional study included 581 men (age 60–90 years) enrolled in the Geelong Osteoporosis Study. Frailty comprised at least three of unintentional weight loss, exhaustion, low physical activity, slowness, and weakness. Serum TAC was measured by quantitative colorimetric determination and expressed as uric acid equivalents (mM). Relationships between TAC (in SD units) and frailty were explored using multivariable logistic regression models. Sociodemographic, anthropometric, and lifestyle variables were tested as potential confounders and effect modifiers. A sensitivity analysis excluded participants ( n = 145) in the upper quartile of TAC, who were likely to have hyperuricemia. Fifty (8.6%) men were frail. There was evidence that higher TAC levels were associated with increased likelihood of frailty ( OR 1.34, 95% confidence interval [CI; 0.99, 1.80]), and this was attenuated after adjustment for age and body mass index (BMI; OR 1.26, 95% CI [0.93,1.71]). No effect modifiers or other confounders were identified. The sensitivity analysis revealed a positive association between TAC and frailty, before and after accounting for age and BMI (adjusted OR 1.79, 95% CI [1.01, 3.17] p = .038). These results suggest a positive association between TAC levels and frailty, supporting the hypothesis that this biomarker could be useful in identifying individuals at risk of frailty. We speculate that a milieu of heightened oxidative stress in frailty may elevate the oxidative stress regulatory set point, raising antioxidant activity. This warrants further investigation.