Salt marshes are anticipated to be exposed to elevated atmospheric CO2 and high salinity due to sea-level rise in the future. This study aims to investigate the effects of elevated atmospheric CO2 and high salinity on microbial communities using intact cores collected from a salt marsh in North Wales, UK. The cores were exposed to two levels of CO2 (ambient vs. ambient +200 ppm) and two levels of salinity (control vs. control + 10 ppt) over a growing season in the Free-Air Carbon Dioxide Enrichment (FACE) facility. We focused on the abundances of bacteria, sulfate reducers (SRB), methanogens and denitrifiers as they play a central role in greenhouse gas emissions. In addition, the activities of extracellular enzymes were determined to assess the effects on microbial activity, followed by Structural Equation Modelling (SEM) to elucidate possible mechanism for the changes we observed. Elevated CO2 significantly increased DOC in pore water for the control salinity treatment during a vigorous growing season (i.e., May - Aug) but not the high salinity treatment. Microbial diversity presented by Shannon’s diversity derived from T-RFLP analysis showed no significant changes except for nirS genes, suggesting potential influence of elevated CO2 on denitrification. Microbial abundances changed substantially for certain functional groups; For example, the abundance of SRB increased both by elevated CO2 and high salinity. In contrast, total bacterial abundance declined under the treatment of high salinity. SEM suggests that elevated CO2 increases DOC in pore-water, which increased sulfate reducers. Salinity plays an additional role in this process to selectively increasing SRB without affecting methanogens. Overall, the results of this study suggest that SRB will play a key role in organic matter decomposition in salt marshes as atmospheric CO2 and salinity increase. This is most likely to be mediated by changes in the quantity and the quality of organic carbon derived from salt marsh vegetation.