Determine if serum levels of tau and BDNF can be used as severity biomarkers in multiple sclerosis (MS).Subjects with MS, older than 18 and younger than 55 years old were included; 74 patients with a diagnosis of relapsing-remitting MS, 11 with secondary-progressive MS, and 88 controls were included. Total tau and BDNF were measured by Western blot.Increased tau and decreased BDNF in MS patients compared with controls was found. Total-tau has a peak in relapsing-remitting MS, the second decile of the multiple sclerosis severity score, and in the lowest expanded disability status scale and is no different than controls for secondary-progressive MS patients and the most severe cases of MS.BDNF is a good biomarker for diagnosis of MS but not for severity or progression. Tau appears to have a more active role in the progression of MS.