Purpose: To establish serum YKL-40 concentrations in patients with endometriosis compared to age-matched healthy subjects. Materials and Methods: This was a cross-sectional clinical study conducted in a tertiary care center. Demographics and serum YKL levels were determined and noted in a total of 63 cases (33 endometriosis patients, 30 healthy controls). Measurement of YKL-40 levels was made using a YKL-40 enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer’s protocol. Results: The mean serum YKL-40 levels of the patient group was 106.0 ± 15.9 (range 23.44 to 382.55) years, while the mean serum YKL-40 levels of the controls was 52.2 ± 7.0 (range 22.35 to 160.0) years (p = 0.003). Conclusions: This is the first study evaluating serum YKL-40 levels in endometriosis. The present results indicate that YKL-40 levels were increased in patients with endometriosis compared to controls. The authors propose that circulating YKL-40 levels could be a novel biomarker for diagnosis and follow-up of endometriosis.