The polls have closed in the by-elections in Wakefield and Tiverton and Honiton.
Both seats were occupied by the Conservatives before their previous deputies resigned in disgrace, leading to by-elections.
Results are expected to be announced overnight.
Polls are seen as a key test for Prime Minister Boris Johnson’s leadership after 148 of his own MPs voted against him in a vote of confidence.
The countdown begins when PM faces a nervous night – follow the latest updates
Asked whether he would consider his position if he lost the two by-elections, the prime minister said: “I will look at the results with interest.”
While “always full of optimism and dynamism,” the prime minister warned, “I think most experienced political observers like you know that midterm by-elections are never necessarily easy for any government.”
In Wakefield, West Yorkshire, former Conservative MP Imran Ahmad Khan resigned after being found guilty of sexually assaulting a 15-year-old boy and imprisoned for 18 months.
Once one of the so-called Red Wall seats, it was won by the Conservatives in the 2019 general election, although Labor is now hoping to get it back.
In Tiverton and Honiton, Devon, Neil Parish resigned after admitting he had seen pornography twice on his phone in the House of Commons.
Liberal Democrats have their sights set on the constituency and should revoke a conservative majority of 24,239.
If the Conservatives lose both by-elections, it would be only the seventh time a government has suffered a double defeat since World War II.
Shabana Mahmood, national coordinator of the Labor campaign, said voters were returning to the party under the leadership of Sir Keir Starmer.
He said: “Labor has campaigned positively with fantastic candidates in both by-elections, but we know that taking the seats requires many Conservative voters to switch to Labor, which is more difficult in by-elections where low turnout is common. .
“Wakefield has been a marginal constituency since the last time Labor won a general election, and the Conservatives have the seat with the largest majority since 2010, making it a difficult task.
“While we await the results of both elections, the message we have heard is clear: many are returning to Labor under Keir Starmer.”
The Liberal Democrats said a significant shift away from the Conservatives to Tiverton and Honiton, one of the party’s safest seats, could see Johnson MPs looking nervously over their shoulder.
Treasury spokeswoman Christine Jardine said: “Never in the history of British politics had such a large majority been annulled in a by-election. We have said throughout this campaign that it is a huge mountain to climb. .
“However, if the Conservative Party loses a significant number of votes tonight in one of its safest seats in the country, tomorrow there will be countless Conservative MPs looking over their nervous shoulders.”