Alex Mitchell has been left out of England's squad for the autumn with a neck problem that places his involvement in the series in doubt.
Mitchell has not played this season because of an injury that has been treated with an injection and Northampton have been unable to provide a timeframe for his return.
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England's first choice No.9 is now battling to play any part in the fixtures against New Zealand, Australia, South Africa and Japan, with his omission from Steve Borthwick's 36-man squad painting a bleak picture for his involvement.
George Ford is also left out as he battles a thigh issue, but he will remain with the group that departs for a training camp in Girona, Spain on Monday to continue his rehabilitation.
Fraser Dingwall is also missing as he nurses a knee injury and with Henry Slade only just about to return from shoulder surgery, England are stretched at centre ahead of New Zealand's visit to Allianz Stadium on November 2.
Slade, an influential figure in defence, is present in the squad and Borthwick must decide whether to allow him to play for Exeter ahead of the All Blacks clash to develop match fitness.
Alex Lozowski's international revival continues with his selection in a second successive squad and the Saracens centre could win his first cap since being axed by Eddie Jones in 2018.
"Naming this squad is an exciting step in our preparations for the Autumn Nations Series and we look forward to working with the players again in the days ahead," Borthwick said on Wednesday.
"Our focus is on thorough preparation and building cohesion as we approach what will be a fiercely competitive series.
"Facing New Zealand in the opening match is a tremendous opportunity for us to test ourselves against one of the best teams in the world.
"Having only played at Allianz Stadium twice in our last 15 games, it will be fantastic to return and play in front of our home crowd.
"The energy and passion of our supporters always give the players an extra boost."
Forwards: Fin Baxter, Ollie Chessum, Dan Cole, Luke Cowan-Dickie, Chandler Cunningham-South, Ben Curry, Tom Curry, Theo Dan, Trevor Davison, Alex Dombrandt, Ben Earl, Charlie Ewels, Ellis Genge, Jamie George, Nick Isiekwe, Maro Itoje, Joe Marler, George Martin, Will Stuart, Sam Underhill.
Backs: Elliot Daly, Immanuel Feyi-Waboso, Tommy Freeman, George Furbank, Ollie Lawrence, Alex Lozowski, Luke Northmore, Harry Randall, Tom Roebuck, Henry Slade, Ollie Sleightholme, Fin Smith, Marcus Smith, Ben Spencer, Freddie Steward, Jack van Poortvliet.
