All of the alterations are in the forwards with Toulouse's Yoann Maestri set to make his first start for France, joining Pascal Papé in the second row.
Jean-Baptiste Poux and Dimitri Szarzewski have been added to the front row with Vincent Debaty and William Servat the players to make way.
Julien Bonnaire has also lost out to the returning Imanol Harinordoquy in a back row which includes Toulouse duo Louis Picamoles and Thierry Dusautoir, the captain of the national side.
Maestri will win his second cap after coming off the replacements bench against the Azzurri, while it will also be cap number 2 for Clermont Auvergne's Wesley Fofana in the centre.
Winger Vincent Clerc remains an obvious danger man with eight tries in nine outings against Ireland, and Francois Trinh-Duc, who played twice against Ireland last August, continues at out-half.
Commenting on the team changes, head coach Philippe Saint-André said: "It's the same squad of 22 except there are four changes in the starting line-up. We wanted to keep things fresh.
"We perhaps worked a little too hard last week and were lacking energy in the first half. We won't play with 15 players, but 22.
"The Irish are are very good in the lineout, so it's logical for Imanol Harinordoquy to come in.
"We need to be more precise with our cleanouts. Yoann Maestri was very good in that area when he came on against Italy.
"These aren't punishments, just adjustments for Ireland. We wanted to have some consistency in the back-line. As soon as we injected some pace we were dangerous. We wanted to see exactly the same back-line in action again."
FRANCE Team & Replacements (v Ireland, 2012 RBS 6 Nations Championship, Stade de France, Saturday, February 11, kick-off 9pm local time/8pm Irish time):
15. Maxime Médard (Toulouse)
16. William Servat (Toulouse)
17. Vincent Debaty (Clermont Auvergne)
18. Lionel Nallet (Racing-Metro 92)
19. Julien Bonnaire (Clermont Auvergne)
20. Morgan Parra (Clermont Auvergne)
21. Lionel Beauxis (Toulouse)
22. Maxime Mermoz (Perpignan)