Wilkinson was carried from the field just 34 minutes into his comeback match for Newcastle against Zurich Premiership opponents Harlequins at The Stoop.
The England and Falcons fly-half had been sidelined for nine weeks recovering from an injury to his left knee, but he flew home to Tyneside with further fitness concerns surrounding the same knee.
England's World Cup hero will undergo a scan and see a specialist in Newcastle on Monday, after which a clearer picture will emerge about whether he will play again this season.
England complete their RBS 6 Nations Championship campaign against Scotland at Twickenham next Saturday, when Wilkinson could conceivably have returned for his first Test appearance since the World Cup final, but that is now inconceivable.
Sir Clive Woodward is said to announce the Lions squad to tour New Zealand on April 11 - they leave for New Zealand on May 25 - and he will be anxiously monitoring developments surrounding Wilkinson.
Wilkinson looked in fine fettle during his time on the pitch, kicking two penalties and a conversion before he was left prone after attempting to tackle Quins prop Ceri Jones.
Newcastle rugby director Rob Andrew refused to be drawn tonight on the possible extent of Wilkinson's latest injury blow, but the initial suggestions were that it might not be as serious as the knee problem which surfaced in early January.
Since the World Cup, Wilkinson has found himself hit by injuries to his shoulder and neck, bicep and knee, raising serious questions about his long-term future in the game.
Andrew said: "Until we actually know, it's pointless making any statement about it.
"He will go back to Newcastle, have a scan, and see the specialist. Having the scan done is the starting point.
"It may be that it's not that serious.
"If you remember the second Lions Test in Melbourne in 2001, when Jonny went off injured in that game, it looked as though he was going to be out for months, but he played in Sydney the following week.
"He looked sharp out there today. His goal-kicking was incredible, his kicking out of hand was good and to me, he was looking good for someone who had been out for nine weeks.'
Harlequins chief executive Mark Evans perhaps summed it up best when he stated: "I feel so sorry for him.
"It is so sad for the lad, and it is incredibly disappointing for him, England, Newcastle, and the Lions.'