Prop Mako Vunipola will not be fit until the end of England's Rugby World Cup pool-stage campaign after suffering a setback with his hamstring injury.
It was initially hoped Vunipola would be fit for England's tournament opener against Tonga on 22 September.
"He's probably going to be right for the third or fourth game," coach Eddie Jones said after England beat Italy 37-0 in Newcastle.
"He just had a little scar tissue which was impairing his movement."
The England boss added: "But that's all been fixed. He's progressing really well now."
|England's Pool C matches|
|26 September||United States|
As expected, Jack Nowell will also miss England's first few games with his long-standing ankle problem.
The Exeter man was also struck down by appendicitis when at the Italy training camp last week, but is now back running.
"Jack Nowell is probably in the same category [as Vunipola]," Jones added.
"They are important players for us so we are prepared to be patient with them."
Vunipola's injury means England will start the World Cup with just four props and the once-retired Joe Marler is most likely to step into the starting loose-head role with Ellis Genge the back up.
Kyle Sinckler, one of two tight-heads alongside Dan Cole, gave fans a scare when he left the field early against Italy but Jones insisted it was nothing to be concerned about.
'We've developed a variety of starting XVs'
The victory in Newcastle was England's third warm-up win, with the only loss coming against Wales in Cardiff.
Jones' side recorded their biggest ever winning margin against Ireland and claimed a comfortable win when they played Wales at home.
But Jones was concerned with more than just the results and has used the games as a chance to experiment with his line-up before the squad flies out to Japan on Sunday.
"The realisation now in world rugby is that you've got to have a number of starting XVs," he added.
"How many times do you get your full squad available? We've been able to use those four games to develop combinations that could be a variety of starting XVs.
"Our World Cup preparation thus far has been very positive. We're growing as a team on and off the field and if we use this next 10 or 12 days efficiently we'll be in an even stronger position."