Boris Johnson faces the potential loss of two Tory seats as votes are counted in by-elections which could lead to further questions about his leadership.
Ballots were cast in Wakefield and Tiverton and Honiton after contests triggered by Conservative MPs resigning in disgrace.
With Labour challenging in the red wall seat in West Yorkshire and the Liberal Democrats hoping to overturn a huge Conservative majority in Devon, defeat for the Tories will heap pressure on Mr Johnson just weeks after 41% of his own MPs said they did not have confidence in him.
Mr Johnson has suggested it would be “crazy” for him to quit if the party lost the two seats, and claimed he was “very hopeful” about the results.
The Prime Minister will be monitoring the results from Rwanda, where he is attending the Commonwealth leaders summit.
Speaking to broadcasters in the capital Kigali, the Prime Minister said: “I’m going to be watching the results with interest but always full of optimism and buoyancy but most seasoned political observers know that by-elections in mid-term are never necessarily easy for any government.”
But despite the Prime Minister’s claims, a senior Tory source acknowledged the situation was looking “extremely difficult” in the Devon seat, where the Conservatives were defending a majority of more than 24,000.
In Wakefield, a Labour campaign source said Sir Keir Starmer’s party would “just” win the contest to replace Imran Ahmad Khan, who quit after being found guilty of sexually assaulting a 15-year-old boy – a crime for which he was jailed for 18 months.
Wakefield was one of the so-called red wall seats won by the Tories in the 2019 general election after being Labour since the 1930s.
In Tiverton and Honiton, Neil Parish – the Tory MP since 2010 – resigned after admitting he had watched pornography on his phone in the House of Commons.
The Liberal Democrats hope to recreate by-election wins in North Shropshire in December and Chesham and Amersham a year ago by taking a Tory heartland seat.
Lib Dem MP Christine Jardine said the party’s candidate Richard Foord had “stood up for his local community” against “a Conservative party which has taken people in Devon for granted”.
“Never in the history of British politics has a majority this big been overturned in a by-election. We’ve said throughout this campaign this is a huge mountain to climb,” she said.
“However, if the Conservative Party lose significant numbers of votes tonight in one of their safest seats in the country, there will be countless Conservative MPs looking over their shoulders nervously tomorrow.”
The Prime Minister urged voters in the rural seat to “stick up for British food and farming” by supporting Tory Helen Hurford, a former head teacher.
Losing the Tory stronghold would be seen as a sign of Mr Johnson’s diminishing electoral appeal after partygate and amid the cost-of-living crisis, and could spark a further backlash against his authority.
The Tories face a steeper challenge in retaining the Wakefield seat, with Labour odds-on favourites to overturn the 2019 Conservative majority of 3,358.
Tory candidate Nadeem Ahmed raised eyebrows by arguing last week that voters should still trust the party after Mr Khan’s sexual assault conviction, just as they still trust GPs despite the crimes of mass murderer Harold Shipman.
Sir Keir has said a victory for candidate Simon Lightwood in the northern constituency “could be the birthplace of the next Labour government”.
If the Conservatives were to lose both by-elections, it would be only the seventh time a government has suffered such a double defeat since the Second World War.
Shabana Mahmood, Labour’s national campaign coordinator, said: “Labour has run positive campaigns with fantastic candidates in both by-elections – but we know that taking the seats requires many Tory voters to switch to Labour, which is harder in by-elections where low turnout is commonplace.
“Wakefield has been a marginal constituency since Labour last won a general election, and the Conservatives hold the seat with the biggest majority since 2010 – making this an uphill task.”
Turnout was 39% in Wakefield – down from 64% in the 2019 general election – and 52% in Tiverton and Honiton, down from 72% in 2019.
