In the search for proteins that might play a role in the pathogenesis of multiple sclerosis (MS), osteopontin (OPN) has been identified as the most prominent cytokine-encoding gene expressed within MS lesions. Here, we report significantly increased OPN protein levels in plasma of relapsing-remitting MS patients. In contrast, OPN protein levels in primary progressive and secondary progressive MS patients were similar to healthy control levels. Interestingly, active relapsing-remitting patients had higher OPN protein levels than patients without relapses.