O'Driscoll started the first two Tests in Durban and Pretoria before injury prevented him from playing a part in the third Test win in Johannesburg on July 4.
The 30-year-old Ireland captain has yet to feature since the defeat at Loftus Versfeld but is set to be thrust back into action on Saturday as Ireland's premier sides go head-to-head in the capital.
"Brian's got enough experience now to play these games fresh from a long break," said Leinster coach Michael Cheika.
"He will have some rustiness, so we don't expect him to go out there and win the game on his own, but it will be very good for him to get his first start at a high level because it will get him up there pretty quickly."
O'Driscoll is likely to be joined in the Leinster starting line up by fellow 2009 Lions Luke Fitzgerald, Rob Kearney, Gordon D'Arcy, Jamie Heaslip and Nathan Hines, who all featured in last weekend's narrow victory over Magners League leaders Edinburgh at Murrayfield.
And with both sides clearly aware of the importance of the fixture, Leinster's Lions could come face-to-face with plenty of team-mates from the recent 10-match tour of the Republic.
Lions captain Paul O'Connell is expected to return to the Munster line up after a slight hamstring strain ruled him out of last weekend's win over the Dragons.
David Wallace is also likely to be included, while Jerry Flannery could make his first appearance since an elbow injury prevented him from travellling to South Africa with four months ago.
Add in the possible presence of John Hayes, Ronan O'Gara, Keith Earls, Donncha O'Callaghan and original Lions selection Alan Quinlan and the latest installment of Leinster versus Munster starts to gain an even more special feel.