Labour MP Pat Glass has resigned as shadow education secretary just two days after being appointed to the role.
Ms Glass was joined by Emma Lewell-Buck who said she was "heartbroken at the state of the party" and could no longer continue as shadow local government minister.
The resignations come after Labour MPs voted overwhelmingly in a confidence vote for Labour leader Jeremy Corbyn to stand down.
Despite the vote Mr Corbyn is refusing to quit, insisting he would not "betray" the 60% of members and supporters who backed him to succeed Ed Miliband.
Angela Eagle - the most senior member of the shadow cabinet to join the mass mutiny - is widely tipped to be chosen to take him on in a leadership contest.
Former foreign secretary Margaret Beckett warned there were "people around Jeremy who are prepared to see the Labour Party split rather than for him to go".
"That is anathema to everybody who thinks that we need to get rid of this Government and the damage that they are doing," she told BBC Radio 4's Today programme.
Dame Tessa Jowell told him it was "absolutely clear that your continued leadership is putting the Labour Party's future in jeopardy and denying millions of people in our country who so desperately need representation by a Labour government".
But shadow chancellor John McDonnell said MPs had to "play by the rules".
"It looks as though we will have a leadership election," he conceded.
"All we are saying to Labour MPs is: play by the rules of our party and, if there is to be a democratic election, respect the decisions of our members."
Mr Corbyn dismissed the confidence vote as having "no constitutional legitimacy" and will address a rally organised by the Momentum movement on Wednesday evening.
He will be joined by Public and Commercial Services union chief Mark Serwotka and Fire Brigades Union general secretary Matt Wrack, who will speak in support of him.
Unite trade union general secretary Len McCluskey was among the first to rally to Mr Corbyn's side after the no-confidence motion.
He accused the MPs of "pointless posturing" and warned they would have to mount a full-blown leadership challenge if they wanted to oust him.
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