Byrne twisted an ankle during the round five match against Perpignan last weekend, but has been included in the starting XV by coach Sean Holley.
Holley said: “We are in a great position as we prepare for the final pool match - we have a home match that we need to win to get a quarter-final place in the European Cup, it doesn't get any more straightforward than that.
“In our way are Leicester Tigers, a side that we know plenty about having faced them in a number of big games in recent seasons, and this one will no doubt be as physical and intense as previous matches, with so much at stake.
"It's a massive game for everybody at the Ospreys. You can't fail to be excited about the prospect of a full house cheering us on."
Ospreys report 17,000 tickets sold already, with tickets still available from the Ticket Office at Liberty Stadium. The Ospreys ticket hotline number is 08700 400004.
Ospreys (v Leicester Tigers, Saturday January 24, Liberty Stadium, kick-off 5.35pm):
15 Lee Byrne
14 Tommy Bowe
13 Andrew Bishop
12 Gavin Henson
11 Shane Williams
10 James Hook
9 Mike Phillips
1 Paul James
2 Richard Hibbard
3 Adam Jones
4 Ian Gough
5 Alun-wyn Jones
6 Ryan Jones (captain)
7 Marty Holah
8 Filo Tiatia
Replacements
16 Huw Bennett
17 Cai Griffiths
18 Lyndon Bateman
19 Tom Smith
20 Jamie Nutbrown
21 Dan Biggar
22 Jonny Vaughton
