Chris Ashton has been ruled out of England's match against Australia on Saturday with a calf injury.
Ashton came off the bench to make his first England outing in four years in the victory over South Africa at the beginning of the month, before starting the New Zealand and Japan fixtures and scoring a try against the All Blacks.
But the Sale Sharks wing was replaced due to injury against the Brave Blossoms and is now set to miss two weeks of action.
"Chris came off with an injury on Saturday," said forwards coach Steve Borthwick. "We investigated the injury and unfortunately he's going to miss a couple of weeks, which means he's clearly unavailable for our game this weekend. He'll return home later today.
"It's only a couple of weeks. It's frustrating. I'm disappointed for him, disappointed for us.
"It's great the work he's done in camp over the last few weeks but hopefully he'll be back on the field very soon."
Borthwick gave the squad an otherwise clean bill of health, with Joe Cokanasiga, who scored a try on debut against Japan, working towards full involvement in training.
"Joe Cokanasiga didn't train with the team today, he trained on his own programme, which is just part of the individual management that we have," added Borthwick.
"But he's fully fit and available for the weekend."
Nathan Hughes is back in the squad following the completion of a six-week ban for punching Gloucester flanker Lewis Ludlow and questioning his punishment on social media.
"Nathan's done well since coming back into camp," said Borthwick. "He trained on Friday, trained again Sunday and trained with the team the last couple of days, doing really well. He's in good shape.
"I think he's worked really hard on his conditioning. Clearly you've got to prepare as well as you possibly can in those circumstances.
"You actually make improvements in lots of areas when you have that opportunity to train like that. And I think Nathan's worked really hard in this period he's had off."