The parliament in Strasbourg, France, is set to back a call by EU leaders for Britain to first agree to divorce terms before striking any new trade deal with the bloc.
MEPs are to vote on the motion a week after British Prime Minister Theresa May formally triggered the process for leaving the EU.
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"We want to have a clear signal that the European Union is united," said German MEP Manfred Weber, the head of the conservative European People's Party (EPP), the parliament's biggest bloc.
"London must understand that no splitting up of the EU position is possible," Weber told reporters on Tuesday.
The guidelines to be voted on Wednesday already have the support of not only the EPP but also of the Socialists and Democrats alliance, as well as the ALDE liberals, the Greens and the leftist parliamentary group GUE.
The parliament will be the first EU institution to take an official stand on the Brexit talks.
"This (vote) is the starting point of a difficult and complex negotiation to define the conditions of the United Kingdom's departure," Parliament President Antonio Tajani said.
The guidelines, which Weber called "red lines", reinforce the draft guidelines unveiled last Friday by EU President Donald Tusk, who represents the member states.
But the 27 countries will not formally approve them until a summit on April 29.
Tusk's guidelines call for "sufficient progress" on divorce terms before a new trade deal is struck, as well as protections of the rights of EU citizens and the border in Northern Ireland.
"The right order for negotiations has to be respected," Weber said.
The Brexit talks have already gotten off to a difficult start after London was alarmed by a clause in the guidelines saying Spain had to be consulted on any post-Brexit trade deal that affects the British outcrop of Gibraltar.
A draft parliamentary resolution said talks on "possible transitional arrangements" for a future deal could begin if "substantial progress" were made towards divorce.
Any transitional period to work out a trade deal after Britain formally leaves the European Union in March 2019 should be limited to three years.
The resolution also insists that Britain must pay to withdraw.
"Until the day you leave, you have to pay your share of the bills," Socialists and Democrats leader Gianni Pittella said at a press briefing in Strasbourg on Tuesday.
And the resolution calls for protecting the rights of the three million European citizens living in Britain, and the one million Britons residing in EU countries.
"Europe's citizens come first," Weber said.
Post-Brexit relations discussed
Opposition to EU migrants helped fuel the Brexit campaign which culminated in the shock vote by Britons last June to leave the bloc.
The EU's chief Brexit negotiator Michel Barnier and European Commission President Jean-Claude Juncker are expected to address the European Parliament after it opens debate at 9:00 am (0700 GMT).
The parliament is likely to hold a vote on any final Brexit deal at the end of 2018 or in early 2019.
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