Dylan Hartley has been left out of England's training squad for their Six Nations opener against Ireland on February 2.
Hartley has not played since December 21 because of a knee injury sustained on Northampton duty and Eddie Jones revealed he has been ruled out of the pre-tournament training camp in Portugal and the trip to Dublin.
"Unfortunately Dylan won't be available for the Ireland game so we won't take him to Portugal, but we are hopeful he will be back later in the Championship," Jones said.
Owen Farrell, who is usually co-captain alongside Hartley, will lead England at the Aviva Stadium 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.
Chris Robshaw has been omitted as he continues his comeback from the knee surgery that forced him to miss the autumn series, but the Harlequins flanker is expected to return later in the tournament.
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.
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.
England will travel to the Algarve on Wednesday to begin their preparations before a 25-strong party will head for Dublin on January 31.
"We are very happy with the squad and have a number of players who have come back from long-term injury," Jones said.
"We are looking forward to getting across to Portugal and having a good ten-day preparation for the Ireland game.
"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.
"To beat Ireland, we need to compete brutally in all the contest areas of the game."
— England Rugby (@EnglandRugby) January 17, 2019
England squad for Six Nations
Forwards: J Clifford (Harlequins), D Cole (Leicester Tigers), L Cowan-Dickie (Exeter Chiefs), T Curry (Sale Sharks), B Earl (Saracens), E Genge (Leicester Tigers), J George (Saracens), N Hughes (Wasps), M Itoje (Saracens), G Kruis (Saracens), J Launchbury (Wasps), C Lawes (Northampton Saints), B Moon (Exeter Chiefs), B Shields (Wasps), K Sinckler (Harlequins), J Singleton (Worcester Warriors), B Vunipola (Saracens), M Vunipola (Saracens), H Williams (Exeter Chiefs), M Wilson (Newcastle Falcons).
Backs: C Ashton (Sale Sharks), M Brown (Harlequins), J Cokanasiga (Bath Rugby), E Daly (Wasps), O Devoto (Exeter Chiefs), O Farrell (Saracens, capt), G Ford (Leicester Tigers), J May (Leicester Tigers), J Nowell (Exeter Chiefs), D Robson (Wasps), H Slade (Exeter Chiefs), B Te'o (Worcester Warriors), O Thorley (Gloucester Rugby), M Tuilagi (Leicester Tigers), B Youngs (Leicester Tigers).