There is a growing body of evidence implicating inflammatory cytokines and brain-derived neurotropic factor (BDNF) in the generation of migraine pain. No previous study evaluated BNDF levels during migraine attacks and there are conflicting results regarding tumor necrosis factor-alpha (TNF-alpha) serum levels. This study compared serum levels of TNF-alpha, soluble TNF receptors 1 and 2 (sTNF-R1 and sTNF-R2), and BDNF during migraine attacks and in headache-free periods. Nine patients with episodic migraine were clinically evaluated during a migraine attack and in a headache-free period. Blood sample of each patient in both occasions was collected and all serum was submitted to TNF-alpha, sTNF-R1, sTNF-R2, and BDNF determination by ELISA. There was no significant difference in the serum levels of TNF-alpha, sTNF-R1 and sTNF-R2 in migraine attack period and headache-free period. BDNF serum levels were significantly higher during migraine attack than in pain-free period. This is the first report showing that BDNF serum levels increase during migraine attack. This reinforces the view that BDNF may be implicated in the physiopathology of migraine.