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The salt content of soil and water in endorheic basins within arid areas greatly restrict agricultural activities. Despite this limitation, these lands are increasingly used to accommodate new settlements and/or agricultural practices. This study focuses on the Laguna El Cuervo closed basin of northern Mexico and its underlying aquifer, which has been found to contain high concentrations of arsenic (As) and fluoride (F). The spatial distribution of As and F, their variations with time, and the impact of drought conditions and land-use changes were investigated using well data collected from a total of 27 wells in 2007, 2010, and 2011 (As data also collected in 2005). Four of these wells were used as monitoring wells. Data also included the As content of 140 surface sediments. Results showed that 54.5 % of the wells surpassed the As limit for drinking water of 0.025 mg L-1 and that 89.0 % surpassed he F limit of 1.5 mg L-1. Spatial analyses identified the areas in the center of the basin with the highest content of contaminants. Principal component and correlation analyses showed a co-occurrence of As and F with r = 0.55 for the 2011 data and 0.59 for the combined data. In contrast, the relationship of As and F concentrations to droughts and changes in land use were not as clearly shown, possibly because of the short time this area has been monitored. The high As and F concentrations in the groundwater may be limiting the availability of water within this basin, especially considering the greater groundwater demand foreseen for the future. Water-conservation practices, such as drip irrigation and artificial groundwater recharge, should be considered to maintain groundwater levels supportive of agricultural practices.