Shanklin was injured in a tackle six minutes from time
Cardiff Blues centre Tom Shanklin will miss the Lions tour as he needs reconstructive surgery on his shoulder that will keep him out for 16 weeks.
The Wales star fell awkwardly after a tackle by the Dragons' Jason Tovey in Wednesday's 26-12 Magners League win.
A scan on Thursday revealed surgery was needed on his right shoulder.
"We are all feeling for him at this difficult time of disappointment and frustration," said Blues chief executive Robert Norster.
"I'm sure I can speak on behalf our the entire Blues family, indeed the entirety of Wales when I offer our sympathies to Tom following his devastating shoulder injury suffered last night that will prevent him travelling with the Lions to South Africa this summer."
Shanklin, 29, won a 2009 Lions call-up following a superb Six Nations that he only played in regularly because of an injury to Gavin Henson, as Wales coach Warren Gatland had wanted to play his first-choice centre partnership of Henson and Jamie Roberts.
The experienced 63-cap Welshman has also been integral part of a hugely successful season for the Blues as coach Dai Young's men won the EDF Energy Cup crown and reached the Heineken Cup semi-finals.
Shanklin joins Munster scrum-half Tomas O'Leary as a pre-Lions tour casualty, while Ireland's Alan Quinlan will find out on Wednesday if he will miss the tour when he goes before a disciplinary panel on eye-gouging charges.
Lions coach Ian McGeechan has said he will take his time before naming replacements, though the party leave for South Africa on 24 May.
It is the second Lions injury setback for double Grand Slam winner Shanklin, who suffered heartbreak early in the 2005 tour of New Zealand.
Fellow Blues team-mate Roberts was told the news of Shanklin's absence from the tour to South Africa moments before appearing on Thursday's Scrum V Radio.
"Absolutely speechless," was Roberts' immediate reaction. "I know I speak on behalf of all the players at the Blues, just how devastated everyone is for Tom.
"I'm sure he's at the bottom of the world right now. As Robert Norster was saying, he's a great character, a real good guy and a good friend and I'm sure he'll be raring to go next season."
But Roberts said the fear of injury cannot enter Lions' heads ahead of the tour as they contend with what can be crucial end-of-season games.
The Blues continue their bid for a place in next season's Heineken Cup by hosting the Lions-littered Irish province in the Magners League on Sunday.
The Welsh team that finishes lowest in the Magners League - the Blues, Dragons or Scarlets - must travel to Italy for a 29 May Heineken Cup play-off game
Roberts said: "As players it is a professional game and each time you pull the jersey on, I know if you're always worrying about the week after you're not going to play to your full potential.
Once we have qualified for the Heineken Cup I won't be putting my Lions up for Blues selection
Blues boss Dai Young
"You've just got to put that jersey on, blank everything else out of your mind and just get on with the job really.
"And I think there's a couple of us Lions boys must play this weekend against Munster and we're fully committed to getting the Blues to the Heineken Cup next year.
"The Lions is in a couple of weeks. We're not focused on that for the moment. We're focused on the job in hand."
McGeechan named Shanklin as one of six Blues players in his squad to face world champions South Africa on their three-Test tour this summer.
The other five are wing Leigh Halfpenny, centre Roberts, prop Gethin Jenkins and back-rowers Andy Powell and Martyn Williams.
Blues coach Young said after his side's win on Wednesday that he would rest his Lions from regional duty once they have qualified for next season's Heineken Cup.
The ex-Lions prop said: "As far as I'm concerned once we have qualified for the Heineken Cup I won't be putting my Lions up for Blues selection and that's important because they have done a great job for us.
"I'm extremely proud of the them and we will look after them to get them on that plane.
"But, at the moment, we still have a job to do and they are 100% behind us as we need to make sure we qualify for Europe next season."
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