Back from international duty, Jamie Heaslip forms a back row partnership with O'Brien and Dominic Ryan, while Scotland international Nathan Hines links up with O'Donoghue in the second row.
Leinster's selected front row includes Ballymena clubman Simon Shawe, a regular for Ireland at AIB Club International level. The 30-year-old, who has played for Ulster at various levels, will relish this opportunity to debut in the Magners League.
Shane Horgan, another of the Ireland internationals available, joins the fit-again Luke Fitzgerald and Niall Morris in an exciting back three.
This will be Fitzgerald's first competitive outing since suffering knee ligament damage against Australia last November. The 22-year-old will be hoping to impress at full-back, a position he deems his favourite.
Meanwhile, new signing Ben Prescott has been named amongst the replacements alongside Ireland hooker John Fogarty.
Argentinian international Mariano Galarza and promising former Ireland Under-20 centre Eamonn Sheridan could also make their competitive debuts off the bench.
Speaking ahead of Friday's game, Nathan Hines said: "Glasgow will be strong. In saying that they do have a few absentees such as Alistair Kellock, Chris Cusiter and (Johnnie) Beattie, while Kelly Brown has gone to Saracens.
"With that, it presents another opportunity for the younger guys to come through and try to claim a scalp.
"Us, we finished top of the table last year and it's their first home game so there's pretty much everything to play for even though they haven't got their strongest team.
"It's quite difficult to analyse teams at this time of year. In my department we try to look at lineouts and try and work out how weak sides are in certain areas, but obviously we haven't much to go on so it's a bit like backyard footy!
"The two pre-season games (that we had) were good preparation for the start of the league proper and obviously they count, but you're not playing for points in pre-season.
"Historically we haven't done very well in Glasgow so it's an opportunity for everyone to get a scalp early on.
"Leicester was an improved performance compared to how we did against Wasps.
"We would have liked to have made bigger strides forward, but as long as we go to Glasgow and produce what we can do on the training pitch and come away with a win, then it doesn't really matter what happens in pre-season. Provided we get our campaign on track."
LEINSTER (v Glasgow Warriors): Luke Fitzgerald; Shane Horgan, Eoin O'Malley, Fergus McFadden, Niall Morris; Isa Nacewa, Isaac Boss; Heinke van der Merwe, Richardt Strauss, Simon Shawe, Nathan Hines, Ed O'Donoghue, Dominic Ryan, Sean O'Brien (capt), Jamie Heaslip.
Replacements: John Fogarty, Jack McGrath, Ben Prescott, Mariano Galarza, Stephen Keogh, Paul O'Donohoe, Ian Madigan, Eamonn Sheridan.