Impaired oocyte quality and oxidative stress might be involved in the pathogenesis of endometriosis-related infertility. To improve our understanding of the role of oxidative stress in this condition, we compare eight oxidative stress markers from each stage, including the simultaneous analysis of lipids, proteins and DNA damage, in the serum and follicular fluid of infertile women with endometriosis and infertile controls undergoing controlled ovarian stimulation for intracytoplasmic sperm injection. In total, 87 serum samples (43 with endometriosis, 44 controls) and 61 follicular fluid samples (29 with endometriosis, 32 controls) free of blood contamination upon visual inspection and presenting granulosa cells alone or granulosa cells plus a retrieved mature oocyte were collected on the day of oocyte retrieval. Total hydroperoxides, malondialdehyde, advanced oxidation protein products, glutathione, superoxide dismutase (SOD) and total antioxidant capacity (TAC) were determined by spectrophotometry, vitamin E by high-performance liquid chromatography and 8-hydroxy-2'-deoxyguanosine (8OHdG) by enzyme-linked immunosorbent assay. The endometriosis group showed higher serum concentrations of glutathione and SOD, lower serum concentrations of TAC and higher follicular concentrations of 8OHdG and vitamin E compared with infertile controls. These data indicate both systemic and follicular oxidative stress in infertile patients with endometriosis. For the first time, we demonstrate the presence of oxidative DNA damage, represented by higher 8OHdG concentrations in the follicular microenvironment of these patients, possibly related to compromised oocyte quality and associated with the pathogenesis of endometriosis-related infertility.