O'Brien will lead the youthful Leinster side from number 8 in a team which also includes returning duo Luke Fitzgerald and Devin Toner.
Fitzgerald, back from the knee ligament injury he sustained against Australia last November, will start at full-back in a back-line which also includes Isa Nacewa.
Toner, who broke his ankle playing for Lansdowne in April, will link up with Trevor Hogan in the second row.
Leinster supporters will get a glimpse of summer signing Heinke van der Merwe who starts in the front row alongside Mike Ross, one of three Ireland internationals in the pack.
The recently-recruited Mariano Galarza has been named on an extended bench which also includes Fergus McFadden, new scrum half Isaac Boss and Stan Wright.
Looking forward to his first game as Leinster head coach, Joe Schmidt said: "The squad is shaping up very well. We've had a few little niggly injuries that are slowing a couple of guys down.
"But the bulk of the squad has come through in good shape after a pretty heavily loaded (training) week down in Wexford.
"You don't know if things are going well until you have a hit-out. That's this Friday.
"It's a fairly young side with a mix of experience. I'm looking forward to seeing some of these younger guys that I didn't see so much of in preparation last season.
"The players are very keen for a game of footy, they just want to put it onto the pitch and try a few things out.
"I'm very keen to see them, and desperately keen that they put in a few characteristic Leinster performances where they show a bit of grit and determination, and at the same time, a little bit of flow to the game."
Tickets for Friday's friendly will be on sale on the night and are also on sale from Spar (Donnybrook), the Leinster Rugby Store (Donnybrook) as well as from Ticketmaster outlets nationwide. Gates open at 5pm and the annual 'Food Market' will return around Donnybrook Stadium for supporters.
For their second and final pre-season game, Leinster will play Leicester Tigers at Welford Road on Friday week (kick-off 7.30pm).
LEINSTER (v London Wasps): Luke Fitzgerald; David Kearney, Eoin O'Malley, Eamonn Sheridan, Isa Nacewa; Ian Madigan, Paul O'Donohoe; Heinke van der Merwe, Richardt Strauss, Mike Ross, Trevor Hogan, Devin Toner, Eoin Sheriff, Paul Ryan, Sean O'Brien (capt).
Replacements (from): Jason Harris-Wright, Jack McGrath, Stan Wright, Mariano Galarza, Dominic Ryan, Isaac Boss, Ian McKinley, Fergus McFadden, Ben Marshall, Michael Keating, Niall Morris.