Stony Coral Tissue Loss Disease (SCTLD) has up to a 99% mortality rate and can affect over 23 species of scleractinian corals. This is an ongoing disease outbreak and the etiology of SCTLD is unknown. As a means to characterize potential SCTLD pathogens, we collected tissue samples from four affected coral species (Dichocoenia stokesii, Diploria labyrinthiformis, Stephanocoenia intersepta, Meandrina meandrites). Tissue samples were from apparently healthy (AH) corals, diseased lesions (DL), and diseased unaffected (DU) corals. Samples were collected from three disease outbreak zones: (1) Lower Florida Keys (SCTLD was not reported, vulnerable zone), (2) Upper Florida Keys (SCTLD was previously present in endemic zone) and (3) Middle Florida Keys (SCTLD was active and prevalent, epidemic zone. From each site, sediment and water samples were also collected to identify potential reservoirs of SCTLD. We used high-throughput sequencing methods to sequence the 16S rRNA gene and bioinformatics analysis to characterize the microbiome of the corals, water, and sediment samples. In the epidemic zone alone shotgun metagenomics was performed