Herpes zoster (HZ, shingles) caused by varicella zoster virus (VZV) reactivation increases stroke risk for up to one-year post-HZ. The underlying mechanisms are unclear, however, the development of stroke distant from the site of zoster (e.g. thoracic, lumbar, sacral) that can occur months after resolution of rash points to a long-lasting, virus-induced soluble factor(s) that can trigger thrombosis and/or vasculitis. Herein, we investigated the content and contributions of circulating plasma exosomes from HZ and non-HZ patient samples. Compared to non-HZ exosomes, HZ exosomes; (1) contained proteins conferring a prothrombotic state to recipient cells, and (2) activated platelets leading to the formation of platelet-leukocyte aggregates. Three-month post-HZ exosomes yielded similar results and also triggered cerebrovascular cells to secrete the proinflammatory cytokines, IL-6 and IL-8. These results can potentially change clinical practice through addition of antiplatelet agents for HZ and initiatives to increase HZ vaccine uptake to decrease stroke risk.