The North-Western part of Argentina is particularly rich in wetlands located in the Puna in an altitude between 3,600 and 4,600 m above sea level. Most of these high-altitude Andean lakes are inhospitable areas due to extreme habitat conditions such as high contents of toxic elements, particularly arsenic. Exiguobacterium sp. S17, isolated from stromatolites in Laguna Socompa, exhibited remarkable tolerance to high arsenic concentration, i.e., it tolerated arsenic concentration such as 10 mM of As(III) and 150 mM of As(V). A proteomics approach was conducted to reveal the mechanisms that provide the observed outstanding resistance of Exiguobacterium sp. S17 against arsenic. A comparative analysis of S17, exposed and unexposed to arsenic revealed 25 differentially expressed proteins. Identification of these proteins was performed by MALDI-TOF/MS revealing upregulation of proteins involved in energy metabolism, stress, transport, and in protein synthesis being expressed under arsenic stress. To our knowledge, this work represents the first proteomic study of arsenic tolerance in an Exiguobacterium strain.