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Flu-hit Great Britain can book their place in the Gillette Tri-Nations final by beating Australia, a feat they have not managed for three years.
Bradford's Iestyn Harris has already been ruled out by the virus that has affected several other players.
Australia, already through to the 27 November final, are without Jason Ryles, Darren Lockyer and Craig Gower.
Third-choice stand-off Scott Hill will play at Wigan as will fit-again second-rower Craig Fitzgibbon.
Canterbury Bulldogs prop Mark O'Meley is set to make his Australia debut against Great Britain after being named on the bench for the Saturday game. The 23-year-old was preferred to full-back Matt Bowen and utility player Shaun Timmins as Tri-Nations back-up.
But the call-up will not surprise Great Britain coach Brian Noble, who had said he would be "stunned" if O'Meley was not picked as cover for Jason Ryles.
If the Lions lose to Australia, they can still reach the final by beating New Zealand at Hull's KC Stadium on 20 November.
But another defeat against the Kangaroos would equal Britain's worst home run against the world champions since they lost seven in a row from 1978-86.
Lions skipper Andy Farrell, who has not missed a match since making a try-scoring debut for Britain against the Kiwis in 1993, insists the players are not weighed down by history.
"We're trying to take a bit of emphasis off how important it is," said the Wigan forward.
"It's about performance and, rather than keep thinking back to how long it's been since we beat Australia, we're just concentrating on the job in hand.
"We did that last week and it paid dividends for us so hopefully can do the same again this week."
Farrell says Britain will take encouragement from their 12-8 defeat at the City of Manchester Stadium, where just 33 seconds were left on the clock when Luke Rooney went over for the match-winning try.
"I thought we played exceptionally well," he said.
"It was all pure grit and tactically we were very good at times but we can get better, especially at taking our opportunities when they arise because you need to against the best side in the world."
Coach Brian Noble will not name his line-up until an hour before kick-off, although the promising half-back combination of Sean Long and Danny McGuire will get another airing.
Great Britain (probable): P Wellens (St Helens); B Carney (Wigan), M Gleeson (Warrington), K Senior (Leeds), S Reardon (Bradford); D McGuire (Leeds), S Long (St Helens); S Fielden (Bradford), T Newton (Wigan), A Morley (Sydney Roosters), A Farrell (Wigan, capt), J Peacock (Bradford), P Sculthorpe (St Helens). Replacements: R Bailey (Leeds), G Ellis (Wakefield), S O'Loughlin (Wigan), M Higham (St Helens),
Australia: A Minichiello (Sydney Roosters); L Rooney (Penrith), S Berrigan (Brisbane), W Tonga (Canterbury), M Sing (North Queensland); S Hill (Melbourne), B Kimmorley (Cronulla); S Webcke (Brisbane), D Buderus (Newcastle, capt), P Civoniceva (Brisbane), C Fitzgibbon (Sydney Roosters), N Hindmarsh (Parramatta), T Carroll (Brisbane). Replacements: C Wing (Sydney Roosters), W Mason (Canterbury), A Ryan (Canterbury), M O'Meley (Canterbury).
Referee: G Black (New Zealand).