BACKGROUND Oxidative stress is associated with the development of several disorders including cardiovascular disease and cancer. Among conditions known to influence oxidative stress, the use of oral contraception (OC) in women has been a matter of ongoing discussion. METHODS A total of 897 eligible and healthy volunteers were recruited from among the patients of 50 general practitioners participating in the ELAN study (Etude Liégeoise sur les ANtioxydants). A subsample consisting of 209 women aged 40–48 years was studied for a comprehensive oxidative stress status (OSS), including the analysis of antioxidants, trace elements and three markers of oxidative damage to lipids. Among 209 subsample, 49 (23%) were OC users (OCU), 119 (57%) non-contraception users (NCU) and 41 (20%) were intrauterine (hormonal and copper) devices users (IUD). RESULTS After adjustment for smoking, systolic and diastolic blood pressure and BMI (or waist circumference), a marked and significant increase in lipid peroxides was observed among OCU women when compared with NCU and IUD users. A cut-off value of 660 µM in lipid peroxides allowed the discrimination of OCU from the two other groups. In contrast, no difference was observed in the plasma concentration of both oxidized low-density lipoprotein (LDL) and their related antibodies. The increased level in lipid peroxides was strongly related to higher concentrations of copper ( r < 0.84; P < 0.0001, cut-off value 1.2 mg/l). When compared with NCU and IUD users, plasma antioxidant defences were significantly altered in OCU women as shown by lower levels of β-carotene (decrease of 39%; P < 0.01) and γ-tocopherol (decrease by 22%; P < 0.01). In contrast, higher concentrations of selenium (increased by 11.8%; P < 0.01) were observed in OCU women. Blood concentrations of vitamin C, α-tocopherol and zinc were unaffected by OC use. CONCLUSIONS The intake of OC significantly increases the lipid peroxidation in women aged 40–48 years. This may represent a potential cardiovascular ...