The cub had liver abnormalities and fluid in its abdomen, but a cause of death will not be known until full necropsy results are available within two weeks.
The cub, believed to be female, died Sunday morning, less than a week after its birth surprised and delighted zoo officials and visitors. Zookeepers had all but given up on the panda mother's chances of conceiving after six years of failed attempts.
"Every loss is hard," National Zoo director Dennis Kelly said. "This one is especially devastating."
This much is known: The cub appeared to be in good condition. It had been drinking its mother's milk. And it wasn't accidentally crushed to death by its mother, which has happened to other panda cubs in captivity. At birth, the cubs are hairless, their eyes are closed and they're about the size of a stick of butter. Their mothers weigh about 1,000 times more.
Native to China, giant pandas have long been the face of the movement to preserve endangered species. A few thousand are believed to remain in the wild, and there are a few hundred in captivity.
Four American zoos have pandas, and several cubs have been born in the U.S., but the bears at the National Zoo are treated like royalty. The zoo was given its first set of pandas in 1972 as a gift from China to commemorate President Richard Nixon's historic visit to the country.
Thousands of people had watched an online video feed of the cub's mother, 14-year-old Mei Xiang, hoping to catch a glimpse of the newborn during its few days of life. Fans from around the country and the world shared their sympathy on social media sites, and many said they shared an emotional connection with the burly, black-and-white bear.
Since the cub's death, Mei Xiang has started eating and interacting with her keepers again. She slept Sunday night while cradling a plastic toy in an apparent show of maternal instinct, Kelly said.
Kelly Parsons of Alexandria, Va., who brought her two young sons to see the pandas Monday, said she felt for Mei Xiang.
"It sounds like the mom is in mourning. Whether you're a parent to an animal or a human being, it's just so sad, the loss of a child," she said.
Suzan Murray, the zoo's chief veterinarian, cautioned that while it may appear the panda is grieving as she cradles the toy, Mei Xiang is a wild animal and her thoughts and emotions are not well understood.
Mei Xiang's only cub, a male named Tai Shan, was born in 2005 and became the zoo's star attraction before he was returned to China in 2010. Since his birth, there had been five unsuccessful attempts to impregnate Mei Xiang, and zoo officials had considered swapping her and her male partner, Tian Tian, for another pair.
Zoo officials said they're focused on Mei Xiang's health but didn't rule out trying to breed her again. At 14, she may have a few more years of fertility remaining. The oldest panda known to have given birth in captivity was 19; pandas can live to their mid-30s.
The mortality rate for panda cubs in the wild is unknown, but in captivity, 26 percent of males and 20 percent of females die in their first year. The zoo's first panda couple, Ling Ling and Hsing Hsing, had five cubs during the 1980s, but none lived more than a few days.
The new cub's liver, about the size of a kidney bean, was harder than usual and discolored, Murray said. The fluid in the cub's abdomen was unusual and could have been a symptom of the liver problem, she said.
There was no evidence of fluid in the cub's lungs, which would suggest pneumonia.
Because Mei Xiang's other cub survived and she appeared to be taking good care of the newborn, zoo officials had been cautiously optimistic. Kelly said he was not aware of anything that could have been done to improve the cub's chances of survival.
The staff was taking the death especially hard because of the work they'd put in over the past six years to produce another cub, Kelly said.
AP Television producer Thomas Ritchie contributed to this report.