Over the past decades, the important topic of environmental sustainability, impact, and security of the fossil fuel supply has stimulated interest in using lignocellulosic feedstocks as biofuel to partially cover energy demands. Among energy no-food crops, giant reed (Arundo donax, L.), a perennial rhizomatous grass has been identified as a leading candidate crop for lignocellulosic feedstock, due to its positive energy balance, and low ecological/agro-management demands. The aim of the present study was to characterize the physiological response of Arundo donax (L.) to artificial soil contamination with three different Cu levels (200, 400, and 800 ppm), and to assess the relationship between plant Cu tolerance and S assimilation rate. The present study not only confirms the ability of Arundo donax L. to cope with Cu stress and therefore to grow in marginal, degraded lands abandoned by mainstream agricultural, but also shows that plant performance might be likely ascribed to a modulation of sulfate metabolism resulting in increased thiols content.