Two presidential aides said Trump was considering forcing out deputy national security adviser Mira Ricardel, but as of Tuesday afternoon, the adviser remained in her West Wing office.
Melania Trump's office took the extraordinary step of issuing a statement saying that Ricardel should be ousted.
While first ladies historically have been known to pressure their husbands over official business, they do not typically issue statements about it.
"It is the position of the Office of the First Lady that she no longer deserves the honor of serving in this White House," Stephanie Grisham, the first lady's spokeswoman, said in a terse statement.
The first lady had complained to the president that she was unhappy with how she was treated by Ricardel, a former Boeing Co executive who worked on the Trump presidential campaign and was picked by National Security Adviser John Bolton to be his deputy earlier this year, two other sources familiar with the White House intrigue told Reuters.
The sources said that Melania Trump explicitly asked the president to oust Ricardel after their dealings over the Africa trip "didn't go well."
One source said that Melania Trump felt that Ricardel tried to short-change the first lady when it came to government resources allocated to support her Africa tour. The sources did not elaborate.
The National Security Council (NSC) had no immediate comment. Ricardel could not be reached for comment.
A smiling Ricardel had a prominent spot at the front of the room at a White House celebration marking Diwali, the Hindu festival of lights, on Tuesday.
Grisham's statement was issued shortly after that event ended. White House spokeswoman Sarah Sanders had no immediate reaction to the first lady's statement.
A source familiar with Ricardel's White House performance said Ricardel has run afoul of much of the NSC staff and "sort of alienated everyone" except for Bolton, who is currently traveling in Asia with Vice President Mike Pence.
Ricardel was also believed to have had a dislike of Defense Secretary Jim Mattis, current and former officials have told Reuters.
One of the sources familiar with the mood at the White House said tensions began building to a crisis point about a month ago and serious efforts were made to defuse the dispute.
MORE UPHEAVALS AT WHITE HOUSE
Meanwhile, three Trump cabinet members - Chief of Staff John Kelly, Homeland Security Secretary Kirstjen Nielsen and Interior Secretary Ryan Zinke - could soon be gone, said sources familiar with internal discussions in the Republican administration.
Turnover among White House personnel paused during the run-up to last week's elections after senior Republicans asked Trump to refrain from firing staff, hoping to minimise perceptions of disorder.
Attorney General Jeff Sessions was forced out by Trump last week just hours after the results came in from the November 6 elections, which handed majority control of the House of Representatives to Democrats.
Trump's first 22 months in office have seen frequent shake-ups. A study this year by the Brookings Institution, a think tank, found Trump's White House has had the highest turnover of senior-level staff of the past five presidents.
Trump was expected to remove Nielsen, a source close to the White House said. Nielsen took the job after Trump made Kelly his chief of staff. But now the president is considering getting rid of both them, the source said.
Zinke has been under investigation for several ethics controversies including travel and a business deal in his home state of Montana, casting doubt on how long he would remain at the helm of the agency.
A final decision on his future could be postponed beyond this week. He is scheduled to travel to California on Wednesday and Thursday to visit communities hit by deadly wildfires, the Interior Department said on Tuesday.
Trump last week said Zinke was doing an “excellent job” but left open the possibility of replacing him. "We're looking at that, and I do want to study whatever is being said," Trump told reporters last week.
Adding to the sense of upheaval at the White House, Special Counsel Robert Mueller was planning to file more indictments in his 18-month investigation of Russian meddling in the 2016 presidential election and possible collusion between Moscow and the Trump campaign, sources said.
