Frogeye leaf spot (FLS), caused by the fungus Cercospora sojina, is one of the most important soybean diseases and can cause great yield losses. Several studies have demonstrated that silicon (Si) enhances the plant antioxidant system, especially when they are subjected to stresses. Thus, this study was designed to evaluate the effect of Si on soybean resistance to FLS, on the antioxidant system, on the concentration of reactive oxygen species and on cellular damage during the infection process of C.sojina. Plants from cultivars Bossier and Conquista, susceptible and resistant to FLS, respectively, were supplied with either 0 (-Si) or 2mm (+Si) and non-inoculated or inoculated with C.sojina. FLS severity was greater for Bossier than for Conquista, regardless of the Si supply, and it was increased by Si for both cultivars. The activities of the most antioxidant enzymes were lower in the +Si plants than in the -Si plants when they were not inoculated. Inoculated plants usually showed an increased enzyme activities and higher concentrations of ascorbate and reduced glutathione than did the non-inoculated plants, regardless of Si supply. At advanced stages of fungal infection, the +Si-inoculated plants from Bossier had higher activity of most antioxidant enzymes and higher concentrations of superoxide and malondialdehyde compared to the non-inoculated plants as a result of an increased oxidative stress. The results from this study provide the first evidence that Si reduces the basal activity of antioxidant enzymes in soybean leaves leading to an increase in host susceptibility to FLS.