For his 72nd Leinster senior cap, O'Brien starts in an all-Ireland international back row alongside Shane Jennings and Kevin McLaughlin.
With a number of players on international duty this weekend, including Heinke van der Merwe who is away with the Springboks, there is a mix of youth and experience to the province's line-up as well as several returning players from injury.
Amongst the players coming back from injury is Isa Nacewa who is named at full-back, with Ian Madigan starting at out-half in his 60th competitive appearance for the province.
Leo Cullen leads the team and will be partnered in the second row by South African Quinn Roux, while Aaron Dundon makes his first appearance at hooker since picking up an injury in the opening round of the league campaign.
The European kingpins' replacements bench includes a panel of Academy graduates, amongst them Ireland second row Devin Toner.
LEINSTER (v Glasgow Warriors): Isa Nacewa; David Kearney, Brendan Macken, Andrew Goodman, Fionn Carr; Ian Madigan, Isaac Boss; Jack McGrath, Aaron Dundon, Jamie Hagan, Leo Cullen (capt), Quinn Roux, Kevin McLaughlin, Shane Jennings, Sean O'Brien.
Replacements: Tom Sexton, Jack O'Connell, Martin Moore, Devin Toner, Jordi Murphy, John Cooney, Noel Reid, Andrew Conway.