While the bays salinity is ideal for oysters and the oyster fishery was at one time the bays most commercially viable, the population has in the last fifty years been devastated. Maryland once had roughly  of oyster reefs. In 2008 there were about . It has been estimated that in pre-colonial times, oysters could filter the entirety of the bay in about 3.3 days; by 1988 this time had increased to 325 days. The harvest's gross value decreased 88% from 1982 to 2007. One report suggested the bay had fewer oysters in 2008 than 25 years earlier.
The primary problem is overharvesting. Lax government regulations allow anyone with a license to remove oysters from state-owned beds, and although limits are set, they are not strongly enforced. The overharvesting of oysters has made it difficult for them to reproduce, which requires close proximity to one another. A second cause for the oyster depletion is that the drastic increase in human population caused a sharp increase in pollution flowing into the bay. The bay's oyster industry has also suffered from two diseases: MSX and Dermo.
The depletion of oysters has had a particularly harmful effect on the quality of the bay. Oysters serve as natural water filters, and their decline has further reduced the water quality of the bay. Water that was once clear for meters is now so turbid that a wader may lose sight of his feet while his knees are still dry.