The threat of heavy metal pollution to public health and wildlife has led to a great interest in the development of effective technologies for heavy metal immobilization in a non-bioavailable form or their conversion into less toxic forms. Organisms subjected to metal exposure in their natural environments have developed resistance mechanisms such us dedicated components and sophisticated homeostasis. Rhodotorula mucilaginosa RCL-11, a pigmented yeast isolated from a fi lter plant of a copper mine in the province of Tucumán, Argentina, supports high concentrations of the heavy metal Cu(II). In order to understand the mechanism involved in resistance to copper in this yeast, a proteomic study was conducted. Identifi cation of differentially expressed proteins was performed. The results obtained show that when R. mucilaginosa RCL-11 was exposed to 0.5 mM copper, differential proteins, involved in cell resistance mechanisms, were expressed. Moreover, copper overload augmented carotenoid biosynthesis in this yeast, modifying at the same time the relative proportion of the pigments produced. Inhibition of the synthesis pathway with diphenylamine suggests an inverse relationship between carotenoid and copper biosorption by R. mucilaginosa RCL-11. The increased activity of superoxide dismutase and catalase measured under inhibition of carotenoid biosynthesis could explain these observations. The change in the relative proportion of the carotenoids torularhodin, torulene, and beta-carotene, as well as the detection of gamma-carotene in the presence of Cu(II) allows to hypothesize that the carotenoids produced by R. mucilaginosa RCL-11 play different roles in the oxidative stress response of this yeast.