The Ospreys will send four of Wales' possible team to face world champions South Africa into battle against EDF Energy Cup opponents London Irish on Sunday.
And Ospreys boss Sean Holley warned: "We do not intend to surrender the trophy lightly."
Centre Gavin Henson, wing Shane Williams, prop Adam Jones and lock Ian Evans all make the Madejski Stadium trip, while Wales captain Ryan Jones is on bench duty.
Full-back Lee Byrne and lock Alun-Wyn Jones - two more likely starters against the Springboks tomorrow week - are rested.
Cup holders the Ospreys will guarantee themselves a third successive Anglo-Welsh semi-final appearance if they topple Irish.
Holley added: "London Irish are a strong side with a very good home record, so we realise the size of the challenge ahead of us.
"Irish play some of the most attack-minded rugby in the Guinness Premiership, and they have a well-drilled, effective set-piece.
"We know that the outcome of the group is in our own hands.
"We've been able to select a 22 that is fresh and confident, with many of the players having points to prove - be it in terms of Ospreys selection or international selection.
"We certainly do not intend to surrender the trophy lightly. We are proud of our record in this tournament, having lost just once in 13 games, and are certainly targeting a third successive trip to Twickenham."
Irish could still make the last four, but their minimum requirement is victory over the Ospreys, with Worcester then coming unstuck against Harlequins at Sixways.
Exiles boss Toby Booth has selected a side that suggests Irish have not given up the ghost, with 11 internationals on view.
The team includes Seilala Mapusua and Sailosi Tagicakibau, who will both be on Pacific Islands duty against England next week, plus an England international half-back pairing of Shane Geraghty and Paul Hodgson.
Booth said: "The Ospreys are among the most talented teams in these islands.
"Last season, we played them at the Liberty Stadium in this competition and know that they like to play a similar style of running, attacking rugby to ourselves.
"An enthralling contest is in prospect."
Gloucester will make the long trip to Newcastle worthwhile if they ground the Falcons on Sunday.
Newcastle, who hope to parade their latest New Zealand recruit Tane Tuipulotu, bowed out of the competition following last week's home loss against Wasps.
And a Gloucester win or draw would take them through, edging out Wasps, although the Londoners can progress if they beat Adams Park visitors Newport Gwent Dragons - preferably with a bonus point - and Newcastle triumph on Tyneside.
Wasps have chosen released England elite squad members Josh Lewsey and Tim Payne in a team captained by number eight Joe Worsley.
And Gloucester include centre Olly Barkley, who was also freed from England duty earlier this week, with fly-half Ryan Lamb back in the side after recovering from a pelvic injury.
Head coach Dean Ryan said: "We haven't played as well as we would have liked, and we recognise that fact, but the positive thing from our point of view is that we can get better.
"We want to do well in every game we play, regardless of the competition, and that obviously makes Sunday's game very important.
"We want to get into a position where we are contesting knockout games."
The Scarlets will clinch a semi-final spot if they beat Franklin's Gardens hosts Northampton tomorrow, although any Scarlets slip-up could see Saints or Saracens nudge them out of contention.
Saracens need a bonus point success at already-eliminated Bristol tomorrow - and hope Northampton sink the Scarlets in a game of no bonus points.
Saracens rugby director Eddie Jones said: "We will find out what the scenarios are at the end of the game.
"The most important things for us is to put in another good performance and keep the momentum building.
"We lost the opening two games of the season, but since then we've won six out of seven and we want to keep that going.
"We've already won at Bristol this season, so there is no reason why we cannot do it again."
Glen Jackson, Hugh Vyvyan and Michael Owen all return after being rested for Saracens' victory over Northampton last weekend, while Bristol field a vastly-experienced side that includes the likes of Mark Regan, Roy Winters, Matt Salter and Dan Ward-Smith.Reuse content