O'Driscoll will fly home from the tour with Adam Jones
The British and Irish Lions will be without Brian O'Driscoll for the tour finale against South Africa in Johannesburg on Saturday.
O'Driscoll suffered concussion in last weekend's bruising 28-25 second Test defeat that ensured the hosts won the series with a match to spare.
The star Irish centre will fly home on Wednesday with Wales prop Adam Jones, who has dislocated a shoulder.
O'Driscoll's absence could earn New Zealand-born Riki Flutey a Lions debut.
Jones' fellow Welsh prop Gethin Jenkins (eye socket) is also ruled out of the third Test after being injured in the clash of heads that has ruled out O'Driscoll.
Tour doctor James Robson says Irish wing Tommy Bowe (elbow) and Welsh centre Jamie Roberts (wrist) have given the Lions hope they will be fit as the tourists bid to end the trip with a victory.
Robson said :"Tommy Bowe and Jamie Roberts continue to be assessed on a daily basis but at this point they are making encouraging progress."
O'Driscoll added: "Being a part of the 2009 British and Irish Lions squad has been one of the highlights of my career.
"We were unbeaten leading into the Test matches and it is a shame that the results in the Tests did not go our way but sport comes down to fine margins at times.
"We could easily have won the first two Tests but it wasn't to be. I have decided to return home to my family this week after a very long season and to ensure I give myself every opportunity to recuperate."
O'Driscoll led the Lions to New Zealand four years ago but his trip ended in the first minute of the opening Test after a controversial spear-tackle by then All Blacks skipper Tana Umaga and Keven Mealamu.
Jones' shoulder dislocation in Pretoria was the result of a charging incident that led to Springbok lock Bakkie Botha being banned for two weeks.
The Osprey prop underwent an operation to have the right shoulder put back into place and the injury is to be assessed by the region after his return .
Jones stated: "It is always disappointing to be ruled out of a Test series through injury but I am proud of what the squad and I have achieved on the tour.
"Personally, I will always remember playing in the two first Tests and especially running on for my debut in the starting XV at Loftus Versfeld. My heart will be with the boys on Saturday."
Jenkins is to remain with the tour party and will be seen again by a surgeon on Friday having already undergone surgery to his injury.
Pre-tour injuries ruled out Jerry Flannery, Tom Shanklin and Tomas O'Leary and a 12-week suspension wrecked Munster flanker Alan Quinlan's tour hopes.
During the tour the O'Driscoll, Jones, Stephen Ferris, Leigh Halfpenny, Lee Byrne, Euan Murray, Ryan Jones and Gethin Jenkins have been lost to the Lions.
Head coach Ian McGeechan is set to name the line-up for the third Test on Thursday.