Objective: Generalized anxiety disorder (GAD) is a prevalent psychiatric disorder. Diagnosis of GAD depends on subjective complaints of patients, thus the need for biological markers is constantly emerging. In this study, we aimed to the investigate diagnostic values of Erythropoietin (Epo) and its receptor (EpoR) levels in drug-naïve patients with GAD. Methods: This study included 45 newly diagnosed drug-naive patients with GAD, aged and sex-matched 30 healthy controls. Medical histories were obtained, and physical examinations and laboratory tests were conducted. Also, the Hamilton Anxiety Rating Scale (HAM-A) was used for all participants. Serum Epo and EpoR levels were measured by ELISA. Results: HAM-A score was significantly higher in GAD patients versus the controls (p < 0.05). While the levels of Epo in patients with GAD were lower than the control patients, EpoR levels were increased in these patients (p < 0.05). Epo/EpoR ratios were significantly lower in the patients with GAD than in the control subjects (p < 0.05). A positive significant correlation was observed between the EpoR level and the HAM-A score (r = 0.755, p < 0.001). However, there was a negative significant correlation between Epo levels and HAM-A score (r = −0.749, p < 0.001).Receiver operator characteristic curve analysis showed high diagnostic performance for Epo and EpoR, areas under curves were 0.901 and 0.912, respectively. Conclusion: This is the first report to investigate the association between serum Epo and EpoR levels in GAD patients. Our results reveal possible diagnostic value of Epo and EpoR. Moreover, Epo therapy may be a good choice for GAD treatment.