Cullen will captain the side and has been named in the second row alongside Devin Toner who impressed as a replacement last Friday.
The third change in the pack sees Sean O'Brien come in as openside flanker, joining Cameron Jowitt and Jamie Heaslip in the back row.
In the back-line, Shane Horgan starts on the right wing while the final change sees Isa Nacewa partner Chris Whitaker at half-back.
Luke Fitzgerald, the hat-trick hero from the Edinburgh game, lines up on the left wing with Girvan Dempsey continuing at full-back.
Looking forward to the televised clash, new Leinster forwards coach Jonno Gibbes said: "The Ospreys will bring a big physical pack, 1 through 8. It's going to be vitally important that we meet them head on and we win the gain-line.
"The guys are focused. They've had a reasonably good win on Friday and they turned up for training on Sunday and Monday focused, with a good attitude and working hard again.
"The Edinburgh result was indicative of four days great preparation and our Ospreys week has been prepared well, which is a good sign."
Over 13,000 tickets have been sold for the Leinster v Ospreys encounter. Tickets are on sale on the Leinster website www.LeinsterRugby.ie, from Spar Donnybrook, the Leinster Rugby Store and usual Ticketmaster outlets.
It will also be possible to purchase tickets at the Ticketmaster outlet on Anglesea Road from 5pm on Friday.
LEINSTER (v Edinburgh): Girvan Dempsey; Shane Horgan, Brian O'Driscoll, Felipe Contepomi, Luke Fitzgerald; Isa Nacewa, Chris Whitaker; Ronan McCormack, Bernard Jackman, Stan Wright, Leo Cullen (capt), Devin Toner, Cameron Jowitt, Sean O'Brien, Jamie Heaslip.
Replacements: Cian Healy, John Fogarty, Malcolm O'Kelly, Stephen Keogh, Shane Jennings, Chris Keane, Rob Kearney.