Josh van der Flier was withdrawn in the first half of last week's win over France due to a groin injury and so O'Brien, who lost his place to the winger, is back in the team.
Munster second row Tadhg Beirne will make his first start in the Six Nations having missed the first two rounds with a knee injury.
The Irish boss, as expected, recalled Rob Kearney and Sean O'Brien while handing Tadhg Beirne his Six Nations debut.
Kearney has overcome a calf injury to take position at full-back pushing Jordan Larmour to the bench. If it was me I'd be concentrating on playing Scotland. We've worked in the (Six Nations) down weeks and we've trained as hard as any team I have seen. He will know his fellow Scarlets teammates very well. "And I know he's incredibly motivated to be as ready as he can be".
Grizzled hooker Rory Best will lead out the side for the final time in the Six Nations as he will retire from the Test arena after the World Cup.
Ireland: 15 Rob Kearney, 14 Keith Earls, 13 Garry Ringrose, 12 Bundee Aki, 11 Jacob Stockdale, 10 Johnny Sexton, 9 Conor Murray; 1 Cian Healy, 2 Rory Best (c), 3 Tadhg Furlong, 4 Tadhg Beirne, 5 James Ryan, 6 Peter O'Mahony, 7 Sean O'Brien, 8 CJ Stander.
Replacements: N Scannell, D Kilcoyne, A Porter, Q Roux, J Conan, K Marmion, J Carty, J Larmour.