Ireland captain O'Connell was a late withdrawal from the opening weekend win with a chest infection but has recovered to start the 2:30pm kick-off at the Aviva Stadium.
O'Mahony and Murray keep their places in the side after impressive performances in the 28-6 win last Sunday.
O'Connell is one of two changes made by Ireland Head Coach Joe Schmidt with Gordon D'Arcy also coming into the side.
Wales have won the last two Six Nations tournaments and go into the game on the back of a 23-15 win over Italy.
When the sides met last season, Munster's Simon Zebo was one of the try-scorers as Ireland recorded a thrilling 30-22 win at the Millennium Stadium.
Munster also face Welsh opposition on Saturday as they host Cardiff Blues in Thomond Park at 7:15pm.
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Ireland team to play Wales in the RBS 6 Nations on Saturday (ko 2:30pm)
15. Rob Kearney (UCD/Leinster) 50
14. Andrew Trimble (Ballymena/Ulster) 51
13. Brian O'Driscoll (UCD/Leinster) 129
12. Gordon D'Arcy (Lansdowne/Leinster) 76
11. Dave Kearney (Lansdowne/Leinster) 3
10. Jonathan Sexton (Racing Metro 92) 39
9. Conor Murray (Garryowen/Munster) 23
8. Jamie Heaslip (Dublin University/Leinster) 61
7. Chris Henry (Malone/Ulster) 10
6. Peter O'Mahony (Cork Constitution/Munster) 20
5. Paul O'Connell (Young Munster/Munster) 88 Capt.
4. Devin Toner (Lansdowne/Leinster) 11
3. Mike Ross (Clontarf/Leinster) 35
2. Rory Best (Banbridge/Ulster) 71
1. Cian Healy (Clontarf/Leinster) 43
16. Sean Cronin (St. Mary's College/Leinster) 31
17. Jack McGrath (St. Mary's College/Leinster) 4
18. Martin Moore (Lansdowne/Leinster) 1
19. Dan Tuohy (Ballymena/Ulster) 8
20. Tommy O'Donnell (UL Bohemians/Munster) 3
21. Isaac Boss (Terenure College/Leinster) 18
22. Paddy Jackson (Dungannon/Ulster) 6
23. Fergus McFadden (Old Belvedere/Leinster) 22