Zookeepers discovered the nine-year-old female in her exhibit area, located in the same building that houses elephants, giraffes, and Nile hippos.
The 600-pound animal showed no signs of disease and seemed normal up until her death, zoo spokesman Robert Hoage said.
The pygmy hippo, a native of Western Africa which is about one-eighth the size of the better-known Nile hippopotamus, can live 40 years or longer in zoos.
A necropsy found pulmonary congestion and a buildup of fluid in the hippo's lungs, Hoage said. A pathology report is expected in a few weeks after further tests.
The pygmy hippo was the last of the specials born at the National Zoo, reports the Washington Post and was the only one kept at the Elephant House.
The loss of the hippo is the latest in a series of mammal deaths at the zoo. But Hoage said the hippo's death does not appear to be related to the others.
Earlier this month two red pandas - animals unrelated to the famed Chinese giant pandas - died after rat poison pellets were buried in their yard.
Late last year, zookeepers had to put down an eight-year-old cheetah and a 24-year-old bobcat. Both were suffering from kidney disease, although officials say the cases were unrelated.
In October, a lion was found dead in its cage one day after it had a complete checkup. A preliminary necropsy found the death was due to an unexplained buildup of blood and fluid in his lungs.
And in September, a gray seal and a giraffe died the same week. The giraffe died of digestive problems which officials said were similar to the symptoms that killed its mate seven months earlier. Digestive problems were cited as the cause of death for the seal.
Zoo officials also have noted with about 3,100 animals at the park, some are born and die everyday.
"Some of these deaths were sad, but not all of them were surprise deaths," said zoo director Lucy H. Spelman. "Animals live and die, but when we lose an animal, it's my job to make sure we're paying the best attention to details."
The Post also reports that a new curator will be appointed to oversee all operations involving animal care.