Background: Chemokine (C-X-C motif) ligand (CXCL)9 and CXCL11 play an important role in the initial phases of autoimmune thyroiditis (AT); however their serum levels in patients with Graves'disease (GD) have never been evaluated in relation to thyroid function and treatment. Methods: To evaluate CXCL9 and CXCL11 serum levels in GD, to relate these parameters to the clinical phenotype, we measured CXCL9 and CXCL11 serum levels in 91 GD patients, 91 AT, 34 non-toxic multinodular goiters (MNG), 31 toxic nodular goiters (TNG) and 91 healthy controls (age- and sex-matched). Results: Mean CXCL9, or CXCL11, levels were higher in GD, in comparison with controls, or euthyroid AT, or MNG, or TNG (*p < 0.05, ANOVA; CXCL9: 274±265, *76±33, *132±78, *87±48, *112±56 pg/mL; CXCL11: 140±92, *64±20, 108±48, *76±33, *91±41 pg/mL; respectively). Hyperthyroid GD had significantly higher CXCL9 or CXCL11 than euthyroid or hypothyroid GD. GD with untreated hyperthyroidism had higher CXCL9 or CXCL11 than hyperthyroid or euthyroid GD under methimazole (MMI) treatment. Comparable CXCL9 and CXCL11 levels were observed in newly diagnosed untreated hyperthyroid GD vs. untreated patients with relapse of hyperthyroidism after a previous MMI course. Conclusions: Serum CXCL9, and CXCL11, levels are associated with the active phase of GD both in newly diagnosed and relapsing hyperthyroid patients. The reduction of serum CXCL9 and CXCL11 levels in treated patients with GD may be related to the immunomodulatory effects of MMI.