The antiviral properties of pressurized liquid extracts (PLE) (acetone, ethanol, and water) obtained from the edible microalga Chlorella vulgaris were evaluated against herpes simplex virus type 1 (HSV-1). None of the extracts tested showed extracellular direct virucidal activity against the virus, although a pretreatment of Vero cells with 75 microg/mL of water and ethanol extracts before virus addition inhibited 70% of the virus infection. Moreover, water and ethanol extracts were able to significantly inhibit the in vitro virus replication, showing IC(50%) values of 61.05 and 80.23 microg/mL respectively. To identify the type of compounds responsible for the antiviral activity found in the water extract, the polysaccharide fraction was isolated. This activity was found to correlate with polysaccharides, because the polysaccharide-rich fraction (46% concentrated) showed higher antiviral activity than the complete water extract. A concentration of 75 microg/mL of this fraction inhibited 90% virus infection when added as a pretreatment and showed an IC(50%) value of 33.93 microg/mL for intracellular virus replication. GC-MS characterization of the ethanol extract showed that the antiviral activity of this extract could be partially related with the presence of phytol, although other compounds could be involved in this activity.