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.
Meanwhile, Ospreys boss Sean Holley has made a massive 13 changes to the team that beat Glasgow 21-18 for this mouth-watering clash with Leinster.
Winger Nikki Walker and lock Alun Wyn Jones are the other players remaining from the side that edged out Glasgow at the Firhill Arena.
Amongst the big-hitters returning to the former champions' line-up are Wales captain Ryan Jones and his international colleagues, full-back Lee Byrne and out-half James Hook.
Star winger Shane Williams is absent from the Ospreys squad due to a dead leg.
Included on the visitors' injury list are Jamie Nutbrown (broken foot), Cai Griffiths (ankle) and Gareth Owen (ankle).
Experienced prop Paul James, who starts on the replacements bench, could set a new Ospreys caps record by coming on for his 102nd appearance.
LEINSTER: 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.
OSPREYS: Lee Byrne; Tommy Bowe, Sonny Parker, Andrew Bishop, Nikki Walker; James Hook, Rhys Webb; Duncan Jones, Huw Bennett, Adam Jones, Alun Wyn Jones, Ian Evans, Jonathan Thomas, Steve Tandy, Ryan Jones (capt).
Replacements: Ed Shervington, Paul James, Ian Gough, Filo Tiatia, Rhodri Wells, Daniel Biggar, Jonny Vaughton.
Referee: Nigel Owens (Wales)
Assistant Referees: George Clancy, Darragh McCormack (both Ireland)
TMO: Dudley Phillips (Ireland)
Say What: Jonno Gibbes (Leinster forwards coach) - "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 had a reasonably good win (over Edinburgh) last Friday and they turned up for training on Sunday and Monday focused, with a good attitude and working hard again.