Edinburgh Rugby second-row Fraser McKenzie could make his Warriors debut from the bench, after joining the club on a short-term deal this week, while full-back Glenn Bryce could make his second appearance for the Warriors and first at Scotstoun.
The Warriors starting XV includes nine internationals, six of which have played for Scotland.
There are two positional switches and four personnel changes to the team which beat Zebre in Parma on Sunday to move to the top of the GUINNESS PRO12.
After scoring two tries in the last game, Peter Murchie is retained at full-back, while Nikola Matawalu moves from scrum-half to the right wing to replace the injured Lee Jones.
Canadian winger DTH van der Merwe continues on the opposite wing, while Richie Vernon and Lyle continue their centre partnership.
After scoring a brace against Zebre and being named man of the match, Peter Horne continues at fly-half, with Ali Price wearing the No. 9 jersey.
In the pack Ryan Grant returns to the side and starts at loose-head in place of Alex Allan, who is on the bench. Pat MacArthur continues at hooker and Rossouw de Klerk comes in for Michael Cusack at tight-head.
Leone Nakarawa moves from Number 8 into the second-row and will partner captain Alastair Kellock in the engine room.
James Eddie and Tyrone Holmes once again start at blind-side and open-side respectively, while Josh Strauss comes in at Number 8, after making a second-half substitute appearance last Sunday following his return from injury.
After scoring for Scotland under-20s last weekend in their win over Wales, prop Zander Fagerson is named on the bench for the first time since November. One of last weekend's try scorers Will Bordill and on loan Canadian back Connor Braid are also named amongst the replacements.
Glasgow Warriors head coach Gregor Townsend said: "We were pleased with our win last weekend, but there are aspects of our game which we need to improve, particularly our work in contact.
"Ospreys have performed consistently well in the league this season and are just four points behind us, so they is a very important game for both sides.
"The intensity levels at training have gone up this week, in the knowledge that we are up against a quality side and because this is a very important game.
"We are looking forward to playing in front of a big crowd at Scotstoun and it should be a cracking match."
14 Nikola Matawalu
13 Richie Vernon
12 Fraser Lyle
11 DTH van der Merwe
10 Peter Horne
9 Ali Price
1 Ryan Grant
2 Pat MacArthur
3 Rossouw de Klerk
4Leone Nakarawa
5 Alastair Kellock (Captain)
6 James Eddie
7 Tyrone Holmes
8 Josh Strauss
Subtitutes
16 Kevin Bryce
17 Alex Allan
18 Zander Fagerson
19 Fraser McKenzie
20 Will Bordill
21 Connor Braid
22 Rory Hughes
23 Glenn Bryce
Not available due to injury: Adam Ashe (neck), Chris Fusaro (ankle), Lee Jones (ankle), Sean Maitland (shoulder), Henry Pyrgos (knee), Gordon Reid (knee), Duncan Weir (arm) and Jon Welsh (hand)