England have suffered a major Six Nations blow due to Billy Vunipola's broken arm while Jack Nowell is one of nine other absentees from last autumn's World Cup.
The Saracens number eight suffered the injury against Racing 92 on Sunday and although no time frame has been given for his return, Vunipola is unlikely to play any part in the forthcoming Six Nations.
"Billy will see a consultant over the coming days to determine the full extent of the injury before undergoing rehabilitation," Saracens said.
Nowell, the Lions wing who is highly rated by Eddie Jones, played for Exeter in Saturday's Champions Cup victory over La Rochelle but is excluded from the 34 names picked for the 2020 Championship.
Also missing from the 32 players who helped England reach the World Cup final are Jack Singleton, Mark Wilson, Dan Cole, Henry Slade, Piers Francis, Joe Cokanasiga, Ben Spencer and Ruaridh McConnochie.
Many of the Japan 2019 casualties are injured.
However, Jones has opted against calling up specialist number eight cover for Vunipola.
Competing to deputise for Vunipola in the back row are Tom Curry, Lewis Ludlam and Ben Earl.
Earl is among eight uncapped players who travel to Portugal on Thursday for a pre-Six Nations training camp with the exciting Saracens prop joined by hooker Tom Dunn, wing Ollie Thorley, centre Fraser Dingwall, full-back George Furbank, lock Alex Moon, prop Will Stuart and fly-half Jacob Umaga.
Umaga, nephew of former New Zealand captain Tana, is included ahead of Marcus Smith who trained with England in the build-up to the World Cup.
England's Six Nations squad
Backs: E Daly (Saracens), O Devoto (Exeter Chiefs), F Dingwall (Northampton Saints), O Farrell (Saracens), G Ford (Leicester Tigers), G Furbank (Northampton Saints), W Heinz (Gloucester Rugby), J Joseph (Bath Rugby), J May (Leicester Tigers), O Thorley (Gloucester Rugby), M Tuilagi (Leicester Tigers), J Umaga (Wasps), A Watson (Bath Rugby), B Youngs (Leicester Tigers).
Forwards: L Cowan-Dickie (Exeter Chiefs), T Curry (Sale Sharks), T Dunn (Bath Rugby), B Earl (Saracens), C Ewels (Bath Rugby), E Genge (Leicester Tigers), J George (Saracens), T Hill (Worcester Warriors), M Itoje (Saracens), G Kruis (Saracens), J Launchbury (Wasps), C Lawes (Northampton Saints), L Ludlam (Northampton Saints), J Marler (Harlequins), A Moon (Northampton Saints), K Sinckler (Harlequins), W Stuart (Bath Rugby), S Underhill (Bath Rugby), M Vunipola (Saracens), H Williams (Exeter Chiefs).
England launch their Six Nations title quest against France in Paris on February 2.
"It is always about winning the next game so we have picked the best squad available," Jones said.
"At the same time we wanted to bring some young players in because we need to keep building our depth so for those new players it's an exciting opportunity for them."
Although no time frame has been given for his return, Vunipola is unlikely to play any part in the forthcoming Six Nations as he comes to terms with the fourth fractured arm of his career.
"Billy will see a consultant over the coming days to determine the full extent of the injury before undergoing rehabilitation," a Saracens statement said.
Vunipola sustained the injury in the sixth minute of the 27-24 victory over Racing that secured crisis-club Saracens a place in the Champions Cup quarter-finals.
The 27-year-old is one of England's most forceful carriers and was a key weapon in last autumn's march to the World Cup final.
Tom Curry is his most likely replacement at number eight for the Six Nations opener against France on February 2, but Vunipola's absence creates the opportunity for Eddie Jones to test a new option in the position.