Carbon (C) cycling in soils is fundamentally linked to the metabolism of microbial communities. Saltwater intrusion into coastal wetlands with sea level rise (SLR) will increase salinity, inundation regime, and marine-derived nutrients (phosphorus, P; sulfur S) with uncertain effects on microbial activities and biogeochemical processes. Freshwater and oligohaline coastal wetlands of the Florida Everglades are particularly vulnerable to increased seawater exposure but differential effects on soil microbial use of C and nutrients need to be quantified. Our objective is to understand how soil microbial extracellular enzyme activities (EEAs) differentially respond to ambient and elevated marine water salinity (10 or 20 ppt) and inundation (soil surface exposed by 5 cm or completely submerged) to affect soil C balance and nutrient acquisition in oligohaline sawgrass peat soils. During initial increase (< 10 d) and longer-term exposure (> 90 d) to elevated salinity and inundation, we measured C- and nutrient-based EEAs and microbial respiration rates. Exposure of soil to elevated marine water altered microbial C and P utilization that varied by depth and time. During initial salinity increase from 10 to 20 ppt, microbial communities showed increased alkaline phosphatase (AKP), decreased acid phosphatase (AP), and increased arylsulfatase (S) activities. After longer-term exposure to salinity and inundation treatments, changes in EEAs in the lowest soil depths (10-20 cm) were detected; AKP activities decreased (P < 0.05) with elevated salinity and cellulase (CEL) activities increased with elevated salinity and inundation (P < 0.05). Increases in seawater likely increased marine-derived P, decreasing microbial demand for P and subsequent AKP production. The interactive effect of salinity and inundation promoted the production of CEL to liberate C from more recalcitrant organic matter in deeper layers of the soil. Changes in microbial EEAs and heterotrophic processing of C may result from a shift in microbial community structure or a change in functional responses with increased salinity and inundation from added seawater. SLR effects on microbial processing of soil C and nutrients are likely to be greatest in the lower depths of soil where the majority of soil C is stored.