The adult cottonmouth does not have any real enemies exept for man and Linguatulid parasites.  Some snakes have been found to be parasitized by linguatulid, Porocephalus crotali, a trematode worm that completely blocks the snakes glottis.  Another trematode know as Leptophullum tamiamiensis affects the cottonmouths kidneys and females uterus. ( Howard K. Gloyd). The Young are frequently eaten by egrets, ibises and small aligators.

Some of there predators include wading birds, horned owls, hawks, eagles, alligators and there own species but these have been reported to be minimal. The main cause of death in Agkistrodon piscivorus is due to starvation.

Cottonmouths have several different anti-predator behaviors.  They are commonly viewed or expressed by humans as a very aggressive snakes but this is probably due to the extreme anxiety or fear people have toward most snakes in general. They will commonly use the escape behavior, defensive posturing, tail vibrations, musk release, mouth gapes, strikes and bites. The snake more often than none will respond to threats by simply trying to escape the path of its predator. It usually never responds with an aggressive defense( bite, or strike) without first trying to escape or using a passive behavior such that would warn, threaten, or distract its predator. (Eric D. Roth & Joel A. Johnson) It has been hypothesized that ant predator behavior varies with body size and increases in body size were associated with a decrease in the level of defensive responses. Research has also been conducted that shows no difference in ant predator behavior between sexes.

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