Under pressure over the appointment of a man whose close ties to the late US sex offender Jeffrey Epstein have come into full focus, Starmer has attempted to change the narrative.
But a demand from Anas Sarwar, leader of the Scottish Labour Party, for him to quit and the departure of a second senior aide in as many days did little to stop the questions over his judgment and ability to govern.
The resignation of communications chief Tim Allan followed the exit of Starmer's closest aide Morgan McSweeney, who said he took responsibility for advising on the appointment of Mandelson to the United Kingdom's top diplomatic role in the US.
Earlier on Monday, the UK leader sought to raise spirits and encourage unity when he addressed staff at his Downing Street office, and he later received messages of support from his top ministers and some potential leadership rivals.
"We must prove that politics can be a force for good," he told them, praising McSweeney as "a friend" who helped change the Labour Party and win the 2024 general election with one of the largest parliamentary majorities in modern UK history.
"I believe it can. I believe it is. We go forward from here. We go with confidence as we continue changing the country."
But Sarwar, speaking in Scotland where polls suggest support for Labour has slumped since the 2024 election, said it was with a heavy heart that he had to defend Scotland and call for a change of leader in the UK capital London.
"The distraction needs to end and the leadership in Downing Street has to change," he told a press conference.
In response, a Downing Street spokesman said Starmer had "a clear five-year mandate from the British people to deliver change, and that is what he will do".
With his statement, Sarwar became the most senior Labour figure to call for Starmer's resignation, and did little to quell a febrile mood in parliament in London's Westminster.
Government borrowing costs rose, reflecting investors' concerns that a more progressive Labour leader, who was willing to borrow and spend more, could take over.
The climb in yields, along with the value of the pound against the euro, later eased after the potential successors came out in Starmer's support.
With Starmer losing his fourth director of communications, his record in government is under scrutiny, including the gaffes and policy U-turns that have tainted his almost two years in power.
"It's painful," said one Labour MP on condition of anonymity.
"It's like watching a fatal car crash in slow motion."
But Starmer received a show of support from his deputy, David Lammy, finance minister Rachel Reeves and foreign minister Yvette Cooper, among others.
Angela Rayner, his former deputy who is seen as a leading leadership candidate, offered him her "full support".
"I urge all my colleagues to come together, remember our values and put them into practice as a team. The Prime Minister has my full support in leading us to that end," she said on X.
The leader of the opposition Conservative Party Kemi Badenoch accused Starmer of being unable to run his government.
"He's like a plastic bag blowing in the wind. We need him to get a grip and if he can't do it then someone else in the Labour Party needs to do that, or they should have an election," she told Sky News.
The new scandal over Mandelson, who was sacked as ambassador to the United States in September, came after files released by the US Justice Department last month included emails suggesting Mandelson had leaked discussions on possible UK asset sales and tax changes to Epstein during the financial crash.
Mandelson is under police investigation for alleged misconduct in office.
Starmer has defended his own actions, accusing Mandelson of creating a "litany of deceit" about his Epstein ties and promising to release documents on how he was appointed.
with PA