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Multiple sclerosis (MS) is an immunoinflammatory disease that affects the central nervous system. Heme oxygenase-1 (HO-1) is one of the three isoforms of the heme oxygenase enzyme that catabolyzes the degradation of heme into biliverdin with the production of free iron and CO. We show in this study that HO-1 expression is reduced in PBMCs of MS patients and that during exacerbation of the disease there is a significant downregulation of this enzyme. We conclude that HO-1 may play a significant role in the maintenance of immune homeostasis which is disrupted in autoimmune disorders, such as MS.