The objective of our pilot clinical, prospective study was to determine the serum levels of mature brain-derived neurotrophic factor, in of women with endometriosis and controls and explore whether mature brain-derived neurotrophic factor is a potential biomarker for the disease. The patients were selected from the Endometriosis Marker Austria prospective cohort study conducted at the tertiary referral certified Endometriosis Center of the Medical University of Vienna. All women underwent laparoscopic surgery because there was a suspicion of endometriosis, or the women had pelvic pain, adnexal cysts, unexplained infertility, or uterine fibroids. Our main outcome parameter was total levels of mature brain-derived neurotrophic factor in serum, measured using ELISA. Our results show that serum levels of mature brain-derived neurotrophic factor are significantly higher in women with endometriosis compared to women without endometriosis. The mean serum protein levels are significantly higher in women with rAFS stage I and II endometriosis, whereas no difference was found in women with stage III and IV endometriosis and controls. Postoperative follow-up at 6-10 weeks revealed that surgical intervention leads to equilibration of the levels of secreted mature brain-derived neurotrophic factor between women with and without endometriosis. The difference between serum mature brain-derived neurotrophic factor levels of women with endometriosis compared to women without endometriosis is independent of menstrual cycle phase and overall self-reported pelvic pain. ROC-curve analysis showed that, the mature brain-derived neurotrophic factor is not a useful biomarker for endometriosis. In conclusion, although women with stage I and II endometriosis have increased levels of mature brain-derived neurotrophic factor in serum compared to controls, the difference is not predictive for the disease. Impact statement Endometriosis is a disease that can have a significant impact on the quality of life of affected women. The gold standard for diagnosis to this day remains visualization through laparoscopic surgery with histological verification. Current studies are attempting to find a biomarker with high sensitivity and specificity, which would bypass the surgery-associated risks and would significantly reduce costs. In an attempt to elucidate whether mature serum BDNF can serve as diagnostic marker for the disease, we compared the levels of the protein in women with endometriosis to endometriosis-free controls. While our results showed that serum concentrations of the mature protein were significantly higher in women with endometriosis, we did not find this marker to have the sensitivity or specificity needed in order to allow a reliable diagnosis.