Up front, Galway man Andrew Browne is promoted from the bench to join Aly Muldowney in the second row.
John Muldoon, who has started all 22 PRO12 fixtures this season, will once again captain the side from a back row with Eoghan Masterson and Eoin McKeon.
The most notable inclusion on the bench is Connacht's most capped player of all time Michael Swift who has worked his way back from injury to take his place amongst the replacements for what could be his last home game before he retires. The 37-year-old, who has played 263 times for the province, is also joined on the bench by Miah Nikora and Shane O'Leary.
Commenting on the team selection and upcoming game, Pat Lam said:
"Losing Darragh (Leader) and Danie (Poolman) in the same week to what is already extensive injury list was obviously a blow but with the culture of team work we have, it's just another opportunity for the next guy to step up and do the job.
"This is probably the most experienced team that we can put out and that will be vital against Ospreys. No man has more experience than Michael Swift. He has worked extremely hard the last few months to get himself back to this position and the preparation, detail and intensity he showed in training this week demonstrated how deserved his inclusion is in the match day squad.
"We all know the enormity of this game. Since pre-season, we have set our sights on a top 6 finish and to be going into round 22 with our ultimate goal still a possibility is very exciting. Its uncharted waters for Connacht Rugby to have so much to play for at this stage of the season and we're really relishing it. Come 5pm tomorrow, we will know our fate. We have no control over other results so all we can do is focus on winning at the Sportsground in front of our supporters to give ourselves the best possible chance of qualification and to finish the season on a massive high."
Connacht team to face Ospreys
15. Tiernan O'Halloran
14. Fionn Carr
13. Robbie Henshaw
12. Bundee Aki
11. Matt Healy
10. Jack Carty
9. Kieran Marmion
1. Denis Buckley
2. Tom McCartney
3. Rodney Ah You
4. Andrew Browne
5. Aly Muldowney
6. John Muldoon (captain)
7. Eoghan Masterson
8. Eoin McKeon
Replacements:
16. Dave Heffernan
17. JP Cooney
18. Finlay Bealham
19. Michael Swift
20. George Naoupu
21. John Cooney
22. Miah Nikora
23. Shane O'Leary
Unavailable/Injured: Jason Harris-Wright, Sean Henry, Ronan Loughney, Nathan White, Mick Kearney, Quinn Roux, Mata Fifita, Willie Faloon, Jake Heenan, Craig Ronaldson, Conor Finn, Dave McSharry, Danie Poolman, Darragh Leader, Mils Muliaina.
Connacht v Ospreys
Saturday May 16th
the Sportsground
Kick off 3pm
Live on S4C
Referee: Marius Mitrea (FIR, 41st competition game)
Assistant Referees: Andy Brace, Nigel Correll (both IRFU)
Citing Commissioner: Tim Lowry (IRFU )
TMO: Seamus Flannery (IRFU)