The immunomodulatory and antiviral effects of an extracellular polysaccharide (EPS-2), produced by a strain of Geobacillus thermodenitrificans isolated from a shallow marine vent of Vulcano Island (Italy), were evaluated. In the present study, we show for the first time that EPS-2 treatment hinder HSV-2 replication in human peripheral blood mononuclear cells (PBMC) but not in WISH cells. In fact, high levels of IFN-alpha, IL-12, IFN-gamma, TNF-alpha, IL-18 were detected in supernatants of EPS-2 treated PBMC. Moreover, this effect was dose-dependent. Taken together, our results confirm that the immunological disorders determined by HSV-2 could be partially restored by treatment with EPS-2.