The Ospreys must beat Leicester Tigers at Liberty Stadium on Sunday to keep their Heineken Cup quarter-final hopes alive.
Tigers lead Pool Two and victory in Wales will leave the two-time champions in pole position ahead of next weekend's showdown with Toulouse.
Reigning Pro12 champions Ospreys are third in Pool Two and are four points behind Toulouse.
The Welsh side, who have failed to reach the quarter-finals of the Heineken Cup for the last two seasons, came through the festive period unbeaten and will be full of confidence after recording the shock of the tournament by beating Toulouse.
Ospreys have lost just one of their last four Heineken Cup matches against Leicester but four of the seven meetings between the two have gone the Tigers' way.
"This is as big as it comes. It's a massive game and is one that we can't afford any slip-ups in," said Ospreys head coach Steve Tandy.
"We've got to be absolutely spot-on in everything we do, our preparation, our attitude and our attention to detail, if we are going to get anything from the match.
"We've done well over the last few weeks to put ourselves in contention in the PRO12 and in Europe, but we realise that we'll need to go up another level this weekend in terms of performance if we want to get the result we need to stay in the competition.
"It's a tough group with six Heineken Cup wins between Leicester and Toulouse, and we are up against teams whose budgets blow us out of the water, but we've got a competitive group of players who will give everything for the cause, who never know when they are beaten, and we are looking forward to this contest.
"They'll come down here confident after some good results of their own lately and we know that we are going to have to match them physically. They've got the advantage in the pool as it stands but there's everything to play for."
In team news, Tom Youngs, Dan Cole and Geoff Parling are among the senior internationals recalled to the Leicester Tigers team.
Forward trio Cole, Youngs and Parling, plus centre Manu Tuilagi, all return in changes to the team that started the Premiership win over Worcester Warriors last week.
Anthony Allen, Marcos Ayerza, Julian Salvi and Jordan Crane also return to the Tigers starting line-up.
Rugby Union betting odds
Ospreys: 15 Richard Fussell, 14 Ross Jones, 13 Tom Isaacs, 12 Andrew Bishop, 11 Eli Walker, 10 Dan Biggar, 9 Kahn Fotuali'i (c), 8 Joe Bearman, 7 Justin Tipuric, 6 Ryan Jones, 5 James King, 4 Ian Gough, 3 Adam Jones, 2 Richard Hibbard, 1 Ryan Bevington.
Replacements: 16 Scott Baldwin, 17 Duncan Jones, 18 Campbell Johnstone, 19 Lloyd Peers, 20 Sam Lewis/Jonathan Thomas, 21 Rhys Webb, 22 Matthew Morgan, 23 Jonathan Spratt.
Leicester Tigers: 15 Mathew Tait, 14 Niall Morris, 13 Manusamoa Tuilagi, 12 Anthony Allen, 11 Adam Thompstone, 10 Toby Flood, 9 Ben Youngs, 8 Jordan Crane, 7 Julian Salvi, 6 Steve Mafi, 5 Geoff Parling, 4 Louis Deacon (c), 3 Dan Cole, 2 Tom Youngs, 1 Marcos Ayerza.
Replacements: 16 Rob Hawkins, 17 Logovi'i Mulipola, 18 Martin Castrogiovanni, 19 Ed Slater, 20 Thomas Waldrom, 21 Sam Harrison, 22 George Ford, 23 Matt Smith.
Date: Sunday, January 13
Venue: Liberty Stadium
Kick-off: 15.00 GMT
Referee: John Lacey (Ireland)