Purpose Our aim was to investigate the serum endocan levels and carotid artery intima-media thickness (CIMT) measurements of pre- and postmenopausal patients to clarify the relationship between the menopausal transition and endothelial injury. Methods This cross-sectional study was conducted on women who were premenopausal and postmenopausal between January 2019 and June 2019. The patients were divided into two groups according to premenopausal (n = 32) and postmenopausal (n = 32) status. Serum endocan levels were assessed by enzyme-linked immunosorbent assay (ELISA). CIMT ultrasonographic measurements were determined. Hormonal and biochemical parameters were measured. The validated Menopause Rating Scale (MRS) questionnaire was used on all women. Results Serum endocan levels were significantly higher in the postmenopausal group than in the premenopausal group (222.90 +/- 121.00 ng/L and 146.62 +/- 41.88 ng/L, p = 0.033, respectively). The mean CIMT was significantly higher in the postmenopausal group than in the premenopausal cohort (0.70 +/- 0.14 mm and 0.58 +/- 0.11 mm, p < 0.001, respectively). A positive correlation was found between body mass index (BMI), systolic blood pressure (SBP), abdominal circumference (AC), and CIMT and postmenopausal serum endocan levels. Serum endocan levels with a cutoff point of 141.14 ng/L identified women with significant CIMT levels with sensitivity of 73.8% and specificity of 77.3%. A positive correlation was found between CIMT and endocan and total MRS scores. Conclusion Serum endocan levels were associated with CIMT during the menopausal transition period. Increased circulating endocan levels can be a predictor of cardiovascular risk in pre- and postmenopausal women.