Results obtained by statistics and geographical information system (GIS) analyses showed that the natural geochemical backgrounds of As and Sb are significantly enhanced in comparison to the Upper Continental Crust (UCC) concentrations, world background levels, and those of industrial sites and historical mining sites. The use of a local enrichment factor (EF) normalized by the mean concentration within the Cala Cala lagoon (CCLAC) demonstrated that using UCC concentrations to calculate EFs (EFUCC) is inadequate for this highly mineralized environment and therefore is not supported. Regarding metals and metalloids, the strong multiplicity of sources in this environment makes it difficult to discriminate between natural and anthropogenic inputs into this endorheic drainage basin, although it is suggested that surficial soils are probably impacted by airborne particulates dispersed from the Vinto (Sb-Sn) smelter, while Lake Uru Uru is influenced by mining activities, particularly drainage waste of the San Jose and Huanuni mines. As a final contribution, a geochemical background and a present-time baseline for Bolivian highlands sediments are provided, which will be helpful for the improvement of environmental legislation and for the future interpretation of geochemistry data in contamination and/or pollution studies in the altiplanic area.