Dylan Hartley is in danger of missing the majority of England's quest to reclaim the Guinness Six Nations title from Ireland due to a knee injury.
Hartley has not played since December 21 after succumbing to what Northampton boss Chris Boyd described as a "grumbly" joint and will miss the pre-tournament training camp in Portugal which begins on Wednesday.
Eddie Jones has tentatively pencilled his co-captain in to return in the third round against Wales on February 23, but England's head coach admits that date might be optimistic.
In the past Jones has taken key players who are recovering from injury to the Algarve to oversee their rehabilitation but Hartley – who is three caps short of reaching the century milestone – will be left at home.
Facing the same scenario is Chris Robshaw, who is close to making his comeback from the knee surgery which ruled him out of the autumn series and could be involved against France on February 10.
"We have taken a completely different approach to the camp this time," said Jones.
"We are specifically focusing on the Ireland game, so we are taking players (to Portugal) who we believe will be available to play against Ireland – no longer-term rehab players.
"Dylan is not going to be available for Ireland. At the outside chance maybe we are looking at Wales.
"It's the same with Robshaw. We are not taking him to Portugal for the same reason – to allow him to rehab and get himself right.
"Hopefully he'll be available for selection further down the track, maybe France."
Owen Farrell, who is co-captain alongside Hartley, will lead England at the Aviva Stadium on February 2 with Jamie George starting at hooker.
"Owen will be captain by himself and he will certainly have great support from a number of senior players," Jones said.
Four uncapped players are present in Gloucester wing Ollie Thorley, Saracens back row Ben Earl, Wasps scrum-half Dan Robson and Worcester hooker Jack Singleton.
Loosehead props Mako Vunipola and Ellis Genge are back after missing the autumn through injury, as are second row Joe Launchbury and number eight Billy Vunipola, with the quartet in line to make their first appearances since the June tour to South Africa.
Harlequins flanker Jack Clifford and Exeter centre Ollie Devoto also return after injury and form has restricted their appearances under Jones.
🌹Congrats to the seven Saracens selected by England to prepare for their Six Nations opener. ⚫🔴 — Saracens Rugby Club (@Saracens) January 17, 2019
Dan Cole and Mike Brown – formerly senior players under Jones until falling out of favour last year – have the opportunity to press their claims in Portugal after being selected in the 35-man squad.
Bath duo Anthony Watson and Jonathan Joseph are missing because of their respective Achilles and ankle injuries.
"Ireland are the best side in the world. They are a very well coached and drilled side and have particular things they do well in the game," Jones said.
"To beat Ireland, we need to compete brutally in all the contest areas of the game.
"Obviously it's a World Cup year so that is always at the back of your mind, but clearly our focus is on beating Ireland.
"They are a good team and deserve all the praise they've been getting. They have a number of exceptional players and a very methodical game plan that maximises the strength of their team."
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