Background: Studies investigating serum vaspin and adiponectin levels in patients with prolactinoma are inconclusive. The aim of this study was to evaluate serum vaspin and adiponectin levels in patients with prolactinoma and healthy controls. Methods: A total of 42 prolactinoma patients (Group 1, 21 patients; Group 2, 21 patients) and 30 healthy controls were enrolled in the study. Group 1 consisted of newly diagnosed patients who were never treated or had not received a dopamine agonist (DA) within 6 months prior to screening. Group 2 consisted of prolactinoma patients who were on DA treatment for at least 6 months at the time of screening. The control group (group 3) consisted of healthy controls. Results. Patients with prolactinoma had higher homeostasis model assessment of insulin resistance and lower quantitative insulin sensitivity check index values in comparison to healthy controls (p<0.001 for both). Serum levels of adiponectin and vaspin were also significantly lower in prolactinoma patients when compared to the control group (p<0.01 and p<0.001, respectively). Following adjustment for confounding factors, the respective odds ratios for prolactinoma in patients in the lower subgroup compared with those in the higher subgroup for adiponectin and vaspin were 2.733 (0.621-12.035; p>0.05) and 5.041 (1.191-21.339; p<0.05). Conclusion: This is the first study to demonstrate the presence of low vaspin levels in patients with prolactinomas. Further studies are needed to help establish the roles of vaspin and adiponectin in prolactinoma patients.