This digitized histological slide collection includes tissue biopsies from wild colonies of Orbicella franksii (OFRA) located at three sites throughout the Dry Tortugas and collected at four time points to capture pre-disease and endemic disease states (September 2021, February 2022, June 2022, and August 2022). Slides were stained with either hematoxylin and eosin stains to highlight tissue morphology or Movat’s pentachrome stain to differentiate connective tissues (mucin, collagen, elastin, myosin). All slides were scanned on a digital slide scanner to a maximum magnification of 40x. All images are in an .svs format. This dataset only includes the raw histological slide collection and associated metadata from biopsied coral colonies. Results from the analysis of the histological slides will be available from partner labs in separate associated datasets.