The experienced trio, who were part of the British and Irish Lions 2013 test winning team in Australia, missed last weekend's opening 26-3 victory in Italy, with O'Brien pulling out after damaging his hamstring in the warm-up.
Hooker Rory Best is also fit to start after coming off with a head injury early in the second half in Rome while prop Cian Healy, who last played in September, returns to the bench for Saturday's game at the Aviva Stadium.
"With so many players returning to the fold, we're probably not going to be as fluid as we'd like. We'll hope to be as accurate as we can be, as clinical as we can be and hopefully that's sufficient," Schmidt told a news conference.
"You can't go full speed for eight weeks so you kind of build your way into the championship by the time you get to critical games. They're all critical, but this one for us particularly is massively important."
Sexton, the only member of the Irish team who plays his club rugby in France with Racing Metro, has had to sit out the last 12 weeks after suffering a series of blows to the head last year.
Despite only being cleared to return to contact training this week, Schmidt said his number 10 was fit and feeling very fresh.
The durable Heaslip missed out last week with a minor knock, a very different story to O'Brien who has only played a full 80 minutes of rugby once since November 2013 when he injured his shoulder and subsequently required two separate surgeries.
While France laboured to a 15-8 home win against Scotland in their opening game, Schmidt said he would not read anything into the performance, saying they possessed a multitude of threats behind the "intuitive" and "instinctive" flyhalf Camille Lopez.
Ireland: 15-Rob Kearney, 14-Tommy Bowe, 13-Jared Payne, 12-Robbie Henshaw, 11-Simon Zebo, 10-Jonathan Sexton, 9-Conor Murray, 8-Jamie Heaslip, 7-Sean O'Brien, 6-Peter O'Mahony, 5-Paul O'Connell (captain), 4-Devin Toner, 3-Mike Ross, 2-Rory Best, 1-Jack McGrath.
Replacements: 16-Sean Cronin, 17-Cian Healy, 18-Martin Moore, 19-Iain Henderson, 20-Jordi Murphy, 21-Isaac Boss, 22-Ian Madigan, 23-Felix Jones.
(Reporting by Padraic Halpin; editing by Justin Palmer)
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