South Sydney's former Bradford forward Sam Burgess has been ruled out of the Great Britain tour to New Zealand and Papua New Guinea.
The 30-year-old suffered a recurrence of a shoulder injury in his club's NRL semi-final defeat by Canberra Raiders in August and is set to undergo surgery.
The loss of Burgess, who made his Great Britain debut as an 18-year-old against the Kiwis in 2007, is a major blow for Wayne Bennett's team as they prepare to embark on the first Lions tour for 23 years.
Rugby Football League rugby director Kevin Sinfield said at a training session at the Manchester Institute of Health and Performance: "We got it confirmed this morning that Sam Burgess will be out of the tour sadly.
"It's very disappointing. He's had an ongoing problem with his shoulder which will probably require surgery.
"He's absolutely gutted, as are we.
"We've seen how special it is to all our players, Sam having been one of the chosen few previously who have worn the shirt and did outstandingly well in it.
"He's a leader and a real big character in that dressing room and on the field he's world class so we'll certainly miss him.
"It will provide somebody else with an opportunity and hopefully they can grab it."
The RFL announced a 16-man England squad for the World Cup Nines, with 11 of them staying on for the Lions tour.
That squad will be boosted by other NRL-based players and representatives from Saturday's Grand Final between St Helens and Salford before it is announced on Monday.
Among the forwards on stand-by is Castleford prop Liam Watts but Sinfield said: "There's still a lot to be decided.
"You'd expect a large contingent to be involved from the Grand Final at the weekend and we'll piece all that together on Sunday morning.
"We've a good idea of where we're at and Wayne is fully across everything. We've had six selectors hard at work pulling squads together, it's probably the most stringent selection process we've ever had."
Sinfield confirmed that former Leeds centre Kallum Watkins, now with Gold Coast Titans, was not selected because of a rib injury and a final decision has yet to be made on the fitness of Wigan loose forward Sean O'Loughlin, who is expected to be named Lions captain.
Meanwhile, Sinfield says newly-crowned Man of Steel Jackson Hastings is in contention after belatedly proving his eligibility.
The Salford half-back was born in Australia but like Warrington stand-off Blake Austin has an English grandparent and he lodged papers to prove his qualification a week ago.
"We'd have liked to have it all confirmed a little bit sooner, especially when you consider how quick Blake was," Sinfield said.
"But we understand where Jackson was at and now he's in contention like everybody else.
"It's a shame he's missed some of the sessions we ran throughout the year but, from my experience of spending a bit of time with him, he's a quite a sociable lad who will fit into most dressing rooms."