Infection is common after stroke and is independently associated with a worse outcome. The predisposition to infection following stroke is in part related to a sympathetically mediated suppression of the peripheral immune response. The teleological explanation for this immune dysfunction is that it serves to prevent autoimmune responses to brain antigens. We believe that the systemic immune response in patients who develop infection, however, thwarts this seemingly protective response and predisposes to central nervous system autoimmunity. These autoimmune responses may mediate, at least in part, the worse outcome associated with post-stroke infection.