Reds captain James Horwill has been ruled out of Friday's clash with the Sharks in Brisbane due to a jaw injury sustained in last weekend's draw with the Western Force.
His omission is one of four personnel changes made to the Reds' starting line-up.
Horwill had been progressing strongly since sustaining his injury in the opening half of their match in Perth, but after receiving further advice from medical staff on Thursday morning it was decided a cautious approach would be the best course of action with the Reds flying to South Africa on Sunday morning for their tough two-game tour of the Republic.
Scrum-half Will Genia will take over the captaincy duties in Horwill's absence while lock Ed O'Donoghue will take his place in the second row for what will be his sixth starting appearance of 2013.
The Reds have made three changes to their back-line with Rod Davies returning to full fitness in place of injured flyer Dom Shipperley (back) and a new centre pairing of Anthony Faingaa at inside centre and Chris Feauai-Sautia.
Faingaa will wear the number 12 jersey for the first since the Reds championship-winning campaign in 2011 with centre Ben Tapuai to be used in a new role from the bench.
In another change, prop James Slipper returns to the starting line-up as the team's vice-captain and tighthead prop with Greg Holmes, in his milestone 100th game for Queensland, moving back to loosehead.
Reds Director of Coaching Ewen McKenzie said the decision to rule Horwill out of the match would ensure the Reds captain would be able to contribute at 100 percent during their upcoming tour to South Africa.
"We gave James plenty of time but ultimately we've chosen to take a safe approach so that he doesn't take any further damage which could see him miss our flight to South Africa on Sunday morning," McKenzie said.
"It is always disappointing when you lose your captain, but Ed has stepped up with every opportunity he has been given this season and he will do a good job for us against the Sharks.
"In terms of Ben Tapuai, he has played all but 51 minutes of our season to date, so we thought it would be a good chance to mix things up and name Anthony at a position he also has a lot of experience at and give Chris a go."
The Reds will be aiming to beat the Sharks for the first time in the McKenzie era while Friday's match will also represent an opportunity to reverse two disappointing results against the South Africans last year, including a Qualifying Final loss at Suncorp Stadium.
"The Sharks are battling a few injuries but they are still stacked with talent across the park, including having a number of Springboks on their bench," McKenzie said.
"It's going to be a huge game and we're also cognisant of the importance of getting an outcome before we get on the plane to South Africa."
Reds: 15 Jono Lance, 14 Rod Davies, 13 Chris Feauai-Sautia, 12 Anthony Faingaa, 11 Digby Ioane, 10 Quade Cooper, 9 Will Genia (c), 8 Jake Schatz, 7 Liam Gill, 6 Eddie Quirk, 5 Ed O'Donoghue, 4 Rob Simmons, 3 James Slipper, 2 Saia Faingaa, 1 Greg Holmes.
Replacements: 16 James Hanson, 17 Albert Anae, 18 Adam Wallace-Harrison, 19 Beau Robinson, 20 Jarrad Butler, 21 Ben Lucas, 22 Ben Tapuai.
Date: Saturday, May 11
Venue: Suncorp Stadium, Brisbane
Kick-off: 19.40 (09.40 GMT, 11.40 SAST)
Referee: Glen Jackson