The Warriors have never won at the Liberty Stadium, but have won four, drawn one and lost one of their six games to date this season against the Welsh regions. They will be boosted by the return of former Scottish skipper Ali Kellock in their second row and will be seeking a significant double over the Ospreys.
"It's a crucial game in terms of securing a Play-Off spot. If we can get a win then it will put a bit of distance between us and them, which will be important with games starting to run out," confessed new Ospreys head coach Steve Tandy..
"We're expecting a difficult night against a tough team who've only lost four games this season and it should be a good game. It's an exciting time for Ospreys rugby, and a fantastic opportunity for some of the young talent we've got coming through the pathway.
"We've seen how players like Beck, Bevington, Webb and Tipuric have made a big step-up this season which has been rewarded with international recognition. In recent months people like Hanno Dirksen, Eli Walker, Joe Rees, James King and Sam Lewis have been exceptional.
"We've got another debutant in Ross Jones at full-back this week, and I think it's fantastic to see so many young players featuring."
One blow for the Ospreys is that former Wales prop Duncan Jones has been ruled out of action for up to eight weeks after damaging knee ligaments
Ospreys: Ross Jones; Hanno Dirksen, Andrew Bishop, Ashley Beck, Eli Walker; Dan Biggar, Rhys Webb; Ryan Bevington, Richard Hibbard, Joe Rees, Ian Gough, James King, Tom Smith (capt), Sam Lewis, Joe Bearman
Replacements: Scott Baldwin, Will Taylor, Aaron Jarvis, Jonathan Thomas, George Stowers, Kahn Fotuali'i, Matthew Morgan, Tom Isaacs