Penicillium thomii PT95 strain is able to form abundant orange, sand-shaped sclerotia in which carotenoids accumulate. We have studied the effects of copper (Cu)-induced oxidative stress on sclerotial differentiation, biosynthesis of some endogenous antioxidants, and activities of a number of the antioxidative enzymes of strain PT95. The association between sclerotial biomass, carotenoid, ascorbate and glutathione contents, and the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductases (GR) were also analyzed in this fungal strain. We found that the oxidative stress induced by Cu was directly dependent on the concentrations of CuSO 4 in the media, with higher CuSO 4 concentrations resulting in higher oxidative stress. Cu-induced oxidative stress in strain PT95 was characterized by the initiation of lipid peroxidation. Under Cu-induced oxidative stress growth conditions, the initiation of exudates and sclerotia in strain PT95, as well as sclerotial maturation, were advanced by 1−2 days. Cuinduced oxidative stress favored sclerotial differentiation and the biosynthesis of endogenous antioxidants, i.e., carotenoids, ascorbate, and glutathione. Comparison of SOD, CAT, and GR activities at 0 and 100 μg/ml Cu revealed a 1.1-, 1.8-, and 1.2-fold increase, respectively, at the higher Cu concentration; comparison of their activities at 100 and 300 μg/ml Cu revealed a 1.4-, 3.1-, and 2.2-fold decrease, respectively, at the higher Cu concentration. APX activity decreased linearly with increasing CuSO 4 concentration. Our results suggest that the ability of the P. thomii PT95 strain to cope with metal stress is related to its ability to trigger an efficient defense against oxidative stress. These findings may contribute to a better understanding of the response mechanisms of sclerotia production in Penicillium strains to metal stress and to better insights into metal-fungi interactions in natural environments.