Work and Pensions Secretary Esther McVey has resigned, saying the Brexit deal "does not honour the result of the referendum".
The MP for Tatton becomes the third minister to resign from her position in the same morning as Dominic Raab and Shailesh Vara.
- Read more: Brexit secretary Dominic Raab resigns over 'very real threat' to UK's integrity
- Read more: Northern Ireland Minister resigns over 'halfway house' Brexit deal
In a statement to the Prime Minister, McVey said she could "not look constituents in the eye" if she had voted for Ms May's Brexit Withdrawl deal.
It comes the day after the Cabinet spent five hours discussing the agreement, that Ms May insisted was "the best that could be negotiated."
"The choices before us were difficult, particularly in relation to the Northern Ireland backstop, but the collective decision of Cabinet was that the government should agree the draft withdrawal agreement and the outline political declaration," she said.
More to follow.