Fungi activity is one of main bio-deterioration factors in the archives and, due to this, its removal is of great importance. Since fungi have different behaviors toward treatment methods, the selection of optimal method for their treatment requires identification of the fungus type, its mechanism and severity of the damage. Malek national library and museum is one of the biggest collections of paper manuscripts in Iran. Assessment of the collection shows fungi effect in almost 540 manuscripts. One of the reported fungi in this collection is Cephalosporium spp and its distribution and effects on aesthetic and structural properties of paper manuscripts have been studied in this research. Analytical samples were selected in the collection and isolated from environment. After cultivation process, active fungi were characterized and distribution and decay of paper caused by Cephalosporium spp were evaluated. Structural properties of papers were assessed by ATR-FTIR and SEM/EDS analysis. The results of this study showed the activity of Cephalosporium spp fungi in 5 percent of investigated samples. The fungus activity resulted in pink and red-to-brown stains on the paper, deterioration of cellulose structure of paper due to cellulose enzymes, damage to surface properties, biologic leaching of inorganic compounds and consequently defects in physical properties.