Desalination brine is a hypersaline byproduct that contains various operational chemicals such as polyphosphonate-based antiscalants. Brine often sinks and flows over the seabed by density currents; therefore, it may affect sediment-water nutrient fluxes and thus microbial activity. We quantified these parameters in brine plumes around two large-scale desalination facilities located in the P-limited Southeastern Mediterranean Sea. The benthic nutrient fluxes and microbial activity were determined using ex-situ core benthocosms, to which we added brine from the dispersion area in excess salinities of ∼3% and 5% above natural levels. A higher influx of dissolved organic phosphorus (∼6-fold) and an efflux of dissolved organic carbon (∼1.7-fold) were measured in the brine-amended cores relative to the controls. This was accompanied by increased oxygen consumption (15%) and increased microbial activity (∼1.5-6.5-fold). Field observations support the results from experimental manipulations, yielding ∼4.5-fold higher microbial activity rates around the brine plume compared to uninfluenced locations. Our results imply that desalination brine can alter sedimentary processes affecting benthic nutrients inventories. Moreover, we show that brine acts as a vector of anthropogenic P, stimulating microbial activity in the sediment-water interface.