After enjoying a long unbeaten run at the start of the season, Harlequins have lost three of their last five games in all competitions, including a league hammering at the hands of Northampton last time out.
However, the men from The Stoop have fonder memories of Europe having beaten Toulouse in their last Heineken Cup outing.
In the back row, Maurie Fa'asavalu returns from injury to take his place on the blindside of the Quins scrum with skipper Chris Robshaw switching sides. Amongst the locks, Charlie Matthews comes in for the injured George Robson.
Up front, new England call-up Joe Marler is forced to contend with a spot in the bench with Mark Lambert taking over the number one shirt. He'll back down next to Joe Gray who comes into the hooking berth.
There is only one change in the back-line but it is a crucial one, with star fly-half Nick Evans returning to the side.
O'Shea is determined not to let the win against Toulouse go to waste but at the same time is most certainly not underestimating Gloucester.
"It has been a pretty tough run for the guys and we have come through it top of the Premiership table and, importantly with this evening in mind, playing for a place in the last eight of the Heineken Cup," he explained.
"As a group we are getting used to playing massive games each week and this is part of our learning curve - every game has something massive riding on it and Saturday is yet another one of those.
"The victory in Toulouse was a seminal moment for the Club, but counts for nothing if it is not backed up on Saturday, and that will set us up for the last pool game next week in Galway.
"Gloucester represent a huge challenge to us, as they are developing one of the most talented squads in the country and play with a huge amount of width but also have a pack who can really mix it up," he added.
Having come unstuck against Worcester last weekend, Gloucester boss Bryan Redpath knows his side are going to have to up their game considerably if they're to come out on top.
"We have to be realistic, Quins have been in great form this season but they've had a couple of tough results recently against admittedly some very good teams," he told the team's official website.
"It's a massive challenge for us going down there. We haven't performed well there in the past so we need to put in a performance that does us credit and gives us a chance to win.
"We need to take our chances against them which we didn't do in the first game at Kingsholm whereas they took everything that came their way that night.
"We were a bit lateral last weekend and we won't have that luxury against Harlequins. It's going to be a real challenge for us but one that we should look forward to."
The Scot has made three changes for the game, two in the back-line and one in the pack.
Full-back Olly Morgan's season-ending injury means that Jonny May will wear the No.15 jersey. Mike Tindall switches from inside to outside centre to accommodate the return of Eliota Fuimaono-Sapolu.
Dario Chistolini will take up the tighthead duties, with Rupert Harden dropping to the bench.
Harlequins: 15 Mike Brown, 14 Tom Williams, 13 Matt Hopper, 12 Jordan Turner-Hall, 11 Ugo Monye, 10 Nick Evans, 9 Danny Care, 8 Nick Easter, 7 Chris Robshaw, 6 Maurie Fa'asavalu, 5 Charlie Matthews, 4 Olly Kohn, 3 James Johnston, 2 Joe Gray, 1 Mark Lambert.
Replacements: 16 Chris Brooker, 17 Joe Marler, 18 Tim Fairbrother, 19 Tomas Vallejos, 20 Luke Wallace, 21 Richard Bolt, 22 Rory Clegg, 23 Tom Casson.
Gloucester: 15 Jonny May, 14 Charlie Sharples, 13 Mike Tindall, 12 Eliota Fuimaono-Sapolu, 11 James Simpson-Daniel, 10 Freddie Burns, 9 Rory Lawson, 8 Luke Narraway (capt) 7 Akapusi Qera, 6 Alasdair Strokosch, 5 Alex Brown, 4 Jim Hamilton, 3 Dario Chistolini, 2 Scott Lawson, 1 Nick Wood.
Replacements: 16 Darren Dawidiuk, 17 Dan Murphy, 18 Rupert Harden, 19 Will James, 20 Matt Cox, 21 Dave Lewis, 22 Ryan Mills, 23 Henry Trinder.
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