"These negotiations have been tough right from the start, but they were always going to get more hard towards the end", May told Sky News on Sunday. "That is uncertainty for people and their jobs", she said.
"A change of leadership at this point isn't going to make the negotiations any easier and it isn't going to change the parliamentary arithmetic", she told Sophy Ridge on Sunday on Sky News.
She defended her deal as "what's right for the people of this country" and "the national interest".
"Some may say that this horse has long bolted, but I say, better late than never".
He has emerged as a favourite to succeed Theresa May as Prime Minister after quitting the Cabinet over the Prime Minister's draft deal to leave the EU.
The PM is braced for a leadership challenge as early as this week after Zac Goldsmith became the 24 MP to submit a letter of no confidence.
Other voices are, like the short-lived former Brexit Secretary Dominic Raab, claiming the game is being fixed, even if he says he won't vote against May.
"I don't think we should look like we're afraid of our own shadow".
"I do think we've been bullied, I do think we've been subject to what is pretty close to blackmail frankly for your viewers at home".
Despite having lost some members of her Cabinet last week, including Brexit secretary Dominic Raab, May used her speech on Monday to stress that she intends to move ahead on the so-called divorce agreement with the European Union, with plans to head to Brussels later this week to thrash out details of the UK's future relationship with the 27-member economic bloc after Britain has formally left in March 29, 2019.
Meanwhile, Labour's Jeremy Corbyn, also speaking on Sky News, touted the possibility of a general election and claimed a second Brexit referendum was "an option for the future".
Next, to the House of Commons.
May's government has promised to publish a range of analyses to help lawmakers decide whether to back her plan for a close trading relationship with the European Union after Brexit in a vote in parliament most likely to happen early next month.
Opposition Labour lawmaker Chuka Umunna, who co-authored the amendment, said he was satisfied with the minister's pledge and would not put the amendment forward for a vote.
Raab told the Andrew Marr Show on BBC that the Brexit deal achieved was "fatally flawed" but could be remedied by just "two or three points" being changed.
Explaining why she is unhappy with the Conservative leadership she once again said she does not like the proposed Brexit deal because it does not give the United Kingdom a voice at the EU.