Coral reefs within the Florida Keys are disappearing at an alarming rate. Coral cover in the Florida Keys National Marine Sanctuary declined by 38% from 1996 to 2000. In 2000, populations of Montastraea annularis at four sites near Molasses Reef within the Florida Keys National Marine Sanctuary and one reef within Biscayne National Park were sampled on a quarterly basis. Anecdotal observations showed corals at Alina's Reef in Biscayne National Park appeared healthy in March, but experienced an acute loss of coral cover by August. Cellular Diagnostic analysis indicated that Alina's Reef corals were in distress: they had been afflicted with a severe oxidative damaging and protein-denaturing stress that affected both the corals and their symbiotic zooxanthellae. This condition was associated with a significant xenobiotic detoxification response in both species, reflecting probable chemical contaminant exposure. These results demonstrate that applying a Cellular Diagnostic approach can be effective in helping to identify stress and its underlying causes, providing diagnostic and prognostic biomarkers of coral health.