Findings from epidemiologic studies of oxidative stress biomarkers and breast cancer have been mixed, although no studies have focused on estrogen receptor-negative (ER−) tumors which may be more strongly associated with oxidative stress. We examined prediagnostic plasma fluorescent oxidation products (FlOP), a global biomarker of oxidative stress, and risk of ER− breast cancer in a nested case-control study in the Nurses’ Health Study and Nurses’ Health Study II. ER− breast cancer cases (n = 355) were matched to 355 controls on age, month/time of day of blood collection, fasting status, menopausal status, and menopausal hormone use. Conditional logistic regression models were used to examine associations of plasma FlOP at three emission wavelengths (FlOP_360, FlOP_320, and FlOP_400) and risk of ER− breast cancer. We did not observe any significant associations between FlOP measures and risk of ER− breast cancer overall; the RR_Q4vsQ1 (95 %CI) 0.70 (0.43–1.13), p_trend = 0.09 for FlOP_360; 0.91(0.56-1.46), p_trend = 0.93 for FlOP_320; and 0.62 (0.37-1.03), p_trend = 0.10 for FlOP_400. Results were similar in models additionally adjusted for total carotenoid levels and in models stratified by age and total carotenoids. Although high (vs. low) levels of FIOP_360 and FIOP_400 were associated with lower risk of ER− breast cancer in lean women (body mass index (BMI) < 25 kg/m²) but not in overweight/obese women, these differences were not statistically significant (p_int = 0.23 for FlOP_360; p_int = 0.37 for FlOP_400). Our findings suggest that positive associations of plasma FlOP concentrations and ER− breast cancer risk are unlikely.