The Labour leadership contest has already cost British families £300 each, Conservatives have warned.
Shadow Chancellor Sir Mel Stride will say taxpayers face a "Burnham penalty" after Sir Keir Starmer's position as Labour leader has been thrown into doubt.
Chaos and speculation around Downing Street - after a seat for Greater Manchester Mayor Andy Burnham to return to Parliament was opened - has been reflected in the bond markets.
Gilt yields, effectively the interest rate on government borrowing, have increased since Labour's poor local election results and movement from potential leadership challengers such as Mr Burnham and former Health Secretary Wes Streeting.
In a speech in Westminster, Sir Mel will say the yield on 10-year gilts is now persistently above five per cent.
New analysis, conducted by the Conservatives, indicates if the spike in yields seen on Friday last week were sustained over a five-year period, it would cost an estimated £5.4billion in total, nearly £300 for every working family.
Sir Mel has described the financial analysis as a "damning verdict by markets on the current Government".
On Monday, yields once rose again, before easing back below levels seen on Friday.
Andy Burnham's path to return to the Commons has already been priced into the markets, Sir Mel Stride will say
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Sir Mel will say: "Andy Burnham is already costing us all money before the by-election writ has even been served.
"Markets do not care about personalities - they care about the fundamentals."
The Shadow Chancellor, at a centre for Policy Studies event, will say a fundamental issues is "the prospect of a new Prime Minister coming in with a plan to borrow even more, to raise anti-growth taxes even higher than those baked into existing plans and with an insufficient understanding of the connection between these actions and market movements".
Sir Mel will say the Prime Minister is not in control of the fiscal direction, and Sir Keir is now under pressure from backbenchers to spend more and hike taxes.
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Sir Mel Stride will described the Tory financial analysis as a 'damning verdict by markets on the current Government'
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"This is a Government increasingly unable to take tough decisions and being pulled to the left – a recipe for more borrowing, more taxes and higher inflation," Sir Mel will say.
Mr Burnham has not yet laid out a detailed manifesto, but last year said it was time to "get beyond this thing of being in hock to the bond markets".
On Monday, the Greater Manchester Mayor indicated he did not plan to scrap Labour's fiscal rules.
He has also faced criticism for his stance on immigration, distancing himself from Home Secretary Shabana Mahmood's plan to raise the qualifying period for indefinite leave to remain.
If the spike in yields were sustained over a five-year period, it would cost an estimated £5.4billion in total
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Robert Jenrick, home affairs spokesman for Reform UK said his comments showed the "King of the North" would have to hike taxes in order to fund migration.
He said: "If Burnham wins, a million low skilled migrants will be allowed to stay and get British citizenship in the next few years.
"And he won't stop the boats. Instead he will put them in bedsits on your street. To pay for it all? He'll have to hike your taxes."
A spokesman for Mr Burnham said: "The Conservatives and Reform represent the failed economics that has sucked wealth and power out of places like Makerfield for 40 years."
They added that Mr Burnham was standing in the by-election to show a different path for communities in Makerfield "making life's essentials more affordable, reindustrialising with good jobs, and building council housing."