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Saltwater intrusion has particularly large impacts on karstic wetlands of the Caribbean Basin due to their porous, carbonate bedrock and low elevation. Increases in salinity and phosphorus (P) accompanying saltwater intrusion into these freshwater, P-limited wetlands are expected to alter biogeochemical cycles along with the structure and function of plant and algal communities. Calcareous periphyton is a characteristic feature of karstic wetlands and plays a central role in trophic dynamics, carbon storage, and nutrient cycling. Periphyton is extremely sensitive to water quality and quantity, but the effects of saltwater intrusion on these microbial mats remain to be understood. We conducted an ex situ mesocosm experiment to test the independent and combined effects of elevated salinity and P on the productivity, nutrient content, and diatom composition of calcareous periphyton from the Florida Everglades. We measured periphyton total carbon, nitrogen, and P concentrations and used settlement plates to measure periphyton accumulation rates and diatom species composition. The light and dark bottle method was used to measure periphyton productivity and respiration. We found that exposure to ~1 g P·m -2 ·yr -1 significantly increased periphyton mat total P concentrations, but had no effect on any other response variable. Mats exposed to elevated salinity (~22 kg salt·m -2 ·yr -1 ) had significantly lower total carbon and tended to have lower biomass and reduced productivity and respiration rates; however, mats exposed to salinity and P simultaneously had greater gross and net productivity. We found strong diatom species dissimilarity between fresh- and saltwater-treated periphyton, while P additions only elicited compositional changes in periphyton also treated with saltwater. This study contributes to our understanding of how the ecologically important calcareous periphyton mats unique to karstic, freshwater wetlands respond to increased salinity and P caused saltwater intrusion and provides a guide to diatom indicator taxa for these two important environmental drivers., (© 2019 by the Ecological Society of America.)