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In desert ecosystems, microbial activity and associated nutrient cycles are driven primarily by water availability and secondarily by nutrient availability. This is especially apparent in the extremely low productivity cold deserts of the McMurdo Dry Valleys, Antarctica. In this region, sediments near streams and lakes provide the seasonally wet conditions necessary for microbial activity and nutrient cycling and thus transfer energy to higher organisms. However, aside from a few studies of soil respiration, rates of microbial activity throughout the region remain unexplored. We measured extracellular enzyme activity potentials (alkaline phosphatase, leucine-aminopeptidase, beta-glucosidase, phenol oxidase, and peroxidase) in soils adjacent to lakes and streams, expecting activity to be primarily related to soil water content, as well as time of season and organic matter supply. Phosphatase and beta-glucosidase activities were higher in shoreline than upland soils; however, potential rates were not correlated with soil water content. Instead, soil organic matter, salinity, and pH were the best predictors of microbial activity. Microbial nutrient limitation metrics estimated from extracellular enzyme activity were correlated with pH and salinity and exhibited similar patterns to previously published trends in soil P and N content. Compared to other terrestrial ecosystems, organic matter specific rates for leucine-aminopeptidase and oxidative enzyme activities were high, typical of alkaline desert soils. Phosphatase activity was close to the global mean whereas beta-glucosidase activity was extremely low, which may reflect the lack of vascular plant derived organic matter in the Dry Valleys. In this cold desert ecosystem, water availability promotes microbial activity, and microbial nutrient cycling potentials are related to soil geochemistry.