Two former prime ministers, Boris Johnson and Liz Truss, are to vote against Rishi Sunak's new Brexit deal for Northern Ireland in a debate later.
Mr Johnson said the deal would either mean Northern Ireland remained tied to the EU, or the UK would not be able to take advantage of Brexit.
Ms Truss believes it would not resolve issues with a deal Mr Johnson struck with the EU in 2019.
Other Brexit-backing Tories are also expected to oppose the deal.
The decision of two former prime ministers to oppose the deal may embolden Brexit-backing Conservative MPs to rebel against the government in Wednesday's vote.
However, the scale of the rebellion is not yet clear, with a key group of Eurosceptic Tories undecided on how they will vote.
Mr Sunak's government is still expected to win the vote with the support of Labour, who have backed the deal.
The vote is on a key part of the deal, known as the Stormont brake, that aims to give a future Northern Ireland Assembly a greater say on how EU laws apply to Northern Ireland.
Under the emergency mechanism assembly members could formally raise concerns over new EU goods legislation, potentially leading to the suspension of the law and arbitration with the EU.
Wednesday's vote is likely to be the only vote MPs get on Mr Sunak's overall Windsor Framework - which he agreed with European Commission President Ursula von der Leyen last month.
Under the Northern Ireland Protocol, inspection and document checks are carried out at Northern Ireland's ports instead of taking place at the Irish border - including goods travelling from Great Britain (England, Scotland and Wales) to Northern Ireland.
The checks apply even if the goods are due to remain in Northern Ireland.
Mr Sunak's new deal is aimed at significantly reducing the number of checks.
The prime minister said the Windsor Framework was proof that the UK has "taken back control", with his spokesperson adding it was "the best deal for the people and businesses of Northern Ireland".
In a statement, Mr Johnson said he found the proposed arrangements of the deal "unacceptable" as the best way for the UK to take back control, and believed it would be best for the government to proceed with the NI Protocol Bill.
That bill would give UK ministers powers in domestic law to make radical unilateral changes to the protocol - but the government says the new deal means there is now no legal justification for doing so.
Mr Johnson agreed the original protocol with the EU in 2019 describing it as "a great deal for our country".
"The proposed arrangements would mean either that Northern Ireland remained captured by the EU legal order - and was increasingly divergent from the rest of the UK - or they would mean that the whole of the UK was unable properly to diverge and take advantage of Brexit," he said.
"That is not acceptable. I will be voting against the proposed arrangements today."
Ms Truss is also said to believe the new framework "fatally impinges" on the UK's ability to diverge from EU rules.
Earlier this week, the Democratic Unionist Party (DUP) said it will vote against the Brexit plans in Parliament this week.
Leader Sir Jeffrey Donaldson said he will continue to work with the government on "outstanding issues" - even though Downing Street said there are no plans for any substantial change to the deal.
The European Research Group (ERG) of Eurosceptic Tory MPs has criticised the Stormont brake, with legal experts advising them it was "practically useless".
The deputy chairman of the group, David Jones, said he would be voting against the deal.
But when asked if the ERG would take a unified position on the deal in Wednesday's vote, he said: "We are not Stalinist."
The vote will take place during Mr Johnson's testimony before the Privileges Committee on Wednesday, where he will be quizzed by MPs over Partygate - a day after he admitted misleading Parliament by accident.
There will be a short break so MPs can vote.
Source: BBC
Image: Reuters
