With several big names already ruled out, Gloucester midfielder Billy Twelvetrees will miss England's June tour of New Zealand.
The centre picked up an ankle knock in the Cherry and Whites' clash with London Irish last weekend.
"It looks like an injury that will be between four to six weeks before it's right, so not great for him, obviously, Billy having had such a good season overall," said Gloucester boss Nigel Davies.
"It's not ligaments, it's a relatively minor injury in his ankle, but it will stop him from playing for between four to six weeks.
"It doesn't need an intervention at this stage. He's had a long period of rugby if you think about the tours as well with England and going with the Lions last summer. So it will give him a good chance to have a good pre-season and hit next season on top form."
Stuart Lancaster is now left with a major selection headache, however. The likes of Tom Croft, Alex Corbisiero, Christian Wade and Jack Nowell are all set to miss out, while Dylan Hartley and Rob Webber nurse injuries. Those involved in the Premiership Final will not feature in the first Test against the All Blacks.
In addition, British and Irish Lions hooker Tom Youngs' wife has fallen ill, and the consensus among domestic and international coaches Richard Cockerill and Stuart Lancaster is that the front-row has made the right call to remain at home next month.