The halophilous cyanobacterium Aphanothece halophytica releases large sums of single type sulfated exopolysaccharide in late logarithmic growth phase in culture. This polysaccharide contained sulfate up to 34.46% of the total moieties in the molecular. As a sulfated polysaccharide that can be biosynthesized in large quantities, however, its antiviral activity has not yet been reported. In this study, we examined effects of exopolysaccharide from A. halophytica Fremy (EPAH) on influenza virus A FM (H1N1) (FM1)-induced pneumonia and reduction in immunocompetence in mice. Previous and simultaneous treatment of EPAH at a dose of 60 mg/kg significantly inhibited pneumonia in FM1-infected mice by 30.4% and 26.7%, respectively. In post-treatment, EPAH displayed its most effective inhibition at a dose of 80 mg/kg with the inhibition rate at 18.69%. Simultaneous treatment of FM1-infected mice with EPAH showed effective improvement on reduction of lymphocyte number with its most effective dose at 60 mg/kg. FM1-infected mice simultaneously received EPAH at a dose of 40 mg/kg also acquired obvious enhancement on release of IL-2 on day 15, and those received EPAH at a dose of 60 mg/kg showed similar enhancement on day 10. Simultaneous treatment with EPAH indicated remarkable recovery or improvement of FM1-induced reduction of IL-1beta level and phagocytic capacity of RES. Simultaneous treatment with EPAH significantly resumed the cytolytic activity of natural killer cells in FM1-infected or CP treated mice at doses of 40 and 60 mg/kg. These results suggested that EPAH is an effective agent against FM1. The mechanisms of its action might be mediated, at least in part, by modulating the host immune system and the interaction positive charges in EPAH and negative charges FM1.