The Nebraska Medical Center said a doctor from Sierra Leone who was being treated for Ebola has died.
The hospital released a statement Monday saying Martin Salia had died "as a result of advanced symptoms of the disease."
Salia was the third Ebola patient to be treated at the hospital and the second person to die of the disease in the United States.
The White House extended condolences to his family and loved ones.
In a statement, the White House said Salia's passing is "another reminder of the human toll of this disease and of the continued imperative to tackle this epidemic on the frontlines."
The World Health Organization Friday reported a slight rise in the Ebola death toll, saying there have been 5,177 deaths among 14,413 confirmed cases worldwide, since the start of the current outbreak.
The WHO said there has been a "steep increase" in the number of cases in Sierra Leone, including 421 new infections reported this past week.
Meanwhile, the hardest hit West Africa country, Liberia, has set a national goal of recording no new cases by Christmas, December 25.
President Ellen Johnson Sirleaf said in a nationwide radio address Sunday that her country's path to recovery will be difficult.
Sirleaf said Liberia's health care system must be better prepared for any future disease epidemic, with sharp improvements also needed in the country's economy and governance.
More than 2,800 of West Africa's 5,165 Ebola deaths have been recorded in Liberia.
On Sunday, U.S. health officials said travelers from Mali will be subject to the same screening and monitoring as people arriving from Liberia, Sierra Leone and Guinea. That includes taking arriving travelers' temperatures and questioning them about their health and possible exposure to the Ebola virus.
Although Mali is not suffering from a widespread Ebola outbreak, there have been a number of confirmed cases there in recent days.