Voters in the northern Brisbane-based seat of Stafford go to the polls on Saturday after the sudden death of former independent MP Jimmy Sullivan on April 9.
Mr Sullivan - who had a 6.83 per cent swing against him in the 2024 election - was expelled from the Labor Party in May 2025 over legal and medical concerns.
The seat has been held by Labor for most of its history, with Mr Sullivan's father Terry serving as the member from 2001 to 2006.
But a political expert warns that could change on Saturday, in a result that would have ramifications for David Crisafulli's ruling LNP government, the Labor opposition and federal politics.
Paul Williams, a political scientist at Griffith University, said he thought it increasingly likely that Fiona Hammond would snatch the seat for the LNP with a predicted vote of 51-52 per cent after preferences were allocated.
Notionally, Labor still holds the seat with a 5.3 per cent two-party preferred margin.
Recent polling showed the LNP on track for an unexpected and historic victory.
With by-election swings towards a sitting government rare, Prof Williams said even a reduction in Labor's margin would technically be a loss for Labor and former premier Steven Miles.
"If (the LNP) bring it from 55 to 53, that's technically a loss for Labor," Prof Williams said.
"They should be winning this seat with 59-60, and we know that's not going to happen.
"If they lose the seat, it's huge. If it was a regional seat, maybe, but to lose a seat in Brisbane for Labor is very consequential."
He said a loss would likely be terminal to Mr Miles' leadership, with shadow treasurer and shadow minister for women Shannon Fentiman best placed to challenge.
Prof Williams also said One Nation had erred by failing to stand a candidate in the urban seat, where the party has historically struggled to get traction.
"They wouldn't win it, but six months ago it would have been impossible and now it's moved from impossible to unlikely," he said.
Where previously the party might have expected to poll between two and four per cent of the vote, on Saturday they might have expected to hit between 12 to 20 per cent or even more.
That sort of result, Prof Williams said, would have almost guaranteed an LNP victory on preferences.
He said the Greens' decision not to allocate preferences would likely only be consequential in the event of a very close result.
On Friday, Mr Miles said the by-election was an opportunity for voters in the seat to send the Crisafulli government a message.
He said the outcome of the election would not change either the government or the leadership of the Labor Party.
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