A structurally unique polyketide, mellisol (1) and 1,8-dihydroxynaphthol 1-O-a-glucopyranoside (3), were isolated from the fungus Xylaria mellisii (BCC 1005). The relative stereostructure of 1 was determined on the basis of X-ray crystallographic data. Compounds 1 and 3 exhibited activity against herpes simplex virus-type 1 with IC50 values of 10.50 and 8.40 lg/mL, respectively. They also showed cytotoxic activity against vero cells at the concentration of 40–50 lg/mL.