Lee Byrne, Tommy Bowe, James Hook, Shane Williams, Mike Phillips and Alun-wyn Jones are all named in the starting line-up, while All Blacks back-rower Jerry Collins is brought into the team after missing the win over Edinburgh in the Magners League last week.
Fellow New Zealand back-rower Marty Holah makes his 50th appearance for the team this weekend.
Ospreys director of coaching Scott Johnson said: “We are travelling to Welford Road, where Leicester haven’t lost at home in a year, so they are clearly a threat, and as finalists last year and winners a couple of times, so they should be.
“We know it will be difficult, we know we need to keep our discipline and we may have to grind it out. Both teams have top-line goal kickers and to give away three points then means you are chasing the game.
“It will be a hard-fought battle, Leicester haven’t conceded too many tries this year so it’ll be up to us to do something special to score.”
Ospreys:
15 Lee Byrne
14 Nikki Walker
13 Tommy Bowe
12 James Hook
11 Shane Williams
10 Dan Biggar
9 Mike Phillips
1 Paul James
2 Huw Bennett
3 Cai Griffiths
4 Alun-wyn Jones
5 Jonathan Thomas
6 Jerry Collins
7 Marty Holah
8 Ryan Jones (c)
Replacements:
16 Richard Hibbard
17 Craig Mitchell
18 Ryan Bevington
19 Ian Gough
20 Filo Tiatia
21 Jamie Nutbrown
22 Andrew Bishop
23 Sonny Parker