Salar de Atacama is one of the largest global reservoirs of natural lithium brines (mean lithium concentration = 1,500 ppm), enabling Chile to be a leading producer of lithium products. This large salar (3,000 km2), located in the Atacama Desert at 2,300 m above sea level, is dominated by microorganisms; however, little is known about the microbes present in the brines associated with this economically important mining process. Here we study lithium as a modulator of microbial richness and diversity in brines representing natural conditions (34.7% salinity) and conditions prior to lithium production with a concentrated brine (55.6% salinity). Brines only supported a single archaeal family (Halobacteriaceae): natural brines included the archaeal genera Halovenus , Natronomonas ,... Haloarcula , and Halobacterium . Concentrated brines included the archaeal genera Halovenus , Halobacterium , and Halococcus . The most abundant bacterial families in natural brine were Rhodothermaceae and Staphylococcaceae; Xanthomonadaceae dominated the bacterial community in the concentrated brine. A comparison of entire microbial community (Archaea and Bacteria) revealed that only seven operational taxonomic units were shared between samples, all of which were Archaea. Further, our results showed that Bacteria were phylogenetically more diverse and rich in the concentrated brine, while archaeal diversity was maximized in the natural brine. The concentrated lithium brines of the Salar de Atacama represent one of the most saline environments described to date (dominated by LiCl). We suggest that elevated concentrations of lithium could greatly modulate microbial diversity and give insights into the adaptive biology of microorganisms required to cope with extremely high concentrations of salts that extend beyond that of NaCl, a far more commonly studied salt.;; Plain Language Summary ;;Lithium is a main component of many of the batteries that we rely on for our daily use. In the last years, nearly 40% of all lithium obtained globally was from a single fragile salt‐lake ecosystem: Salar de Atacama in the Atacama Desert of northern Chile. This salar has extremely saline waters called brines (dominated by NaCl, aka table salt), which are naturally highly concentrated in lithium and concentrated in evaporation ponds. In total, concentrated brines has a salinity of 55.6% (ocean salinity = 0.3%), representing one of the most saline environments described on Earth to date (dominated by lithium chloride). Our research has shown that concentrated brines support life and are dominated by hundreds of species of microorganisms. Due to saline stress these “extremophiles” have developed very special (and previously undescribed) strategies to survive in this lithium soup. These results have implications beyond Earth: they have marked implications for our understanding for the potential for life on Mars, where liquid water is known to occur as brine. Although lithium production has clear economic importance, our results show that we should consider how we will preserve these unusual ecosystems that act as reservoirs of unique microbial life.