George Kruis has been ruled out of England's last two matches this autumn because of a calf injury sustained against New Zealand on Saturday.
Kruis was replaced by Charlie Ewels in the 66th minute of the 16-15 defeat at Twickenham and will not play any part in the remaining Quilter Internationals against Japan and Australia.
It is a bitter blow to the Saracens lock who has impressed so far this autumn, not least for his expertise as a line-out caller – a role that will now be performed by Maro Itoje or Ewels.
Itoje, Ewels, Elliott Stooke and Courtney Lawes are the second rows included in the 30-man squad that is to assemble at England's Surrey training base on Tuesday afternoon to begin preparations for the visit of Japan.
Kruis, meanwhile, will target a return from his latest injury set-back in time for Saracens' Champions Cup double header against Cardiff Blues next month.
"George has got a calf injury. It's highly unlikely he'll be available again for a few weeks – anywhere from four to eight weeks," head coach Eddie Jones said.
"It's a calf strain. He did it during the game. It's disappointing because he'd been out injured for a while and was just coming back into form.
"We'll certainly miss him, but it opens the door for Courtney Lawes or Charlie Ewels to come in. It's testing the depth of the squad."
Dylan Hartley is expected to be available despite being replaced at half-time against New Zealand because of a thumb injury, but Manu Tuilagi is unlikely to be risked as he builds fitness in the wake of a groin strain.
"Manu came in yesterday (Monday) and did a little bit of running," said Jones, who reiterated that he will name his strongest team for Saturday.
"But again, it's highly unlikely we'll risk him his week. If we can, we'll try to get him right for Australia."
Jones wants England to show no mercy against the team he coached to the greatest upset in rugby history when South Africa were stunned in Brighton at the 2015 World Cup.
"We want to smash Japan and it's important our players have that mindset because it's one of those tricky games," Jones said.
"It's a game you should win, you're expected to win and if you go in with anything but an aggressive, physical mindset you get caught out. Japan have a record of showing how that can be done."
Jones advised Japan to "go to the temple and pray" in the immediate aftermath of a controversial defeat by New Zealand, but he recalls his time with the minnows fondly.
"I loved it. I loved the players, loved the time there. I'm so pleased that Japan is now a serious member of the rugby community because they weren't before," Jones said.
"That's why they've got this fixture. They've just played New Zealand. They played Australia recently, they've played Italy, they're getting all these top fixtures now.
"They've got a World Cup there in 2019 so it's been great for them."
