Scientists fear the pythons could disrupt the food chain and upset the Everglades' environmental balance in ways difficult to predict.
"The effects of declining mammal populations on the overall Everglades ecosystem, which extends well beyond the national park boundaries, are likely profound," said John Willson, research scientist at Virginia Tech and co-author of the study.
Tens of thousands of Burmese pythons, which are native to Southeast Asia, are believed to be living in the Everglades, thriving in the warm, humid climate.
Many of the snakes are believed to have been released by their owners and others to have escaped from pet shops during Hurricane Andrew in 1992. They have been reproducing ever since.
Burmese pythons can grow to be 26 feet long and more than 200 pounds, and have been known to swallow animals as large as alligators. They and other constrictor snakes kill their prey by coiling around it and suffocating it.
The National Park Service has counted 1,825 Burmese pythons that have been caught in and around Everglades National Park since 2000. One, captured earlier this month, was 16.4 feet long and weighed 156 pounds.
For the study, researchers drove 39,000 miles along Everglades-area roads from 2003 through 2011, counting wildlife spotted along the way and comparing the results with surveys conducted on the same routes in 1996 and 1997.
The researchers found staggering declines in animal sightings: a drop of 99.3 percent among raccoons, 98.9 percent for opossums, 94.1 percent for white-tailed deer and 87.5 percent for bobcats.
Along roads where python populations are believed to be smaller, declines were lower but still notable.
Rabbits and foxes, which were commonly spotted in 1996 and 1997, were not seen at all in the later counts.
Researchers noted slight increases in coyotes, Florida panthers, rodents and other mammals, but discounted that finding because so few were spotted overall.
"The magnitude of these declines underscores the apparent incredible density of pythons in Everglades National Park," said Michael Dorcas, a professor at Davidson College in North Carolina and lead author of the study.
Although scientists cannot definitively say that the pythons are killing off the mammals, the snakes are the prime suspect.
The increase in pythons coincides with the mammals' decline, and the drop appears to grow in magnitude with the size of the snakes' population in an area.
A single disease appears unlikely to be the cause since several species have been affected.
The report said that the effect on the overall ecosystem is hard to predict.
Declines among bobcats and foxes, which eat rabbits, could be linked to pythons' feasting on rabbits. On the flip side, declines among raccoons, which eat eggs, may help some turtles, crocodiles and birds.
Scientists point with concern to what happened in Guam, where the invasive brown tree snake has killed off birds, bats and lizards that pollinated trees and flowers and dispersed seeds. That has led to declines in native trees, fish-eating birds and certain plants.
In 2010, Florida banned private ownership of Burmese pythons. Earlier this month, U.S. Interior Secretary Ken Salazar announced a federal ban on the import of Burmese pythons and three other snakes. Salazar said yesterday that the study shows why restrictions were needed.
"This study paints a stark picture of the real damage that Burmese pythons are causing to native wildlife and the Florida economy," he said.