England centre Henry Slade will miss the Six Nations with a broken leg and ankle damage that will keep the Exeter star out for four months.
The 22-year-old will be unable to take part in the early throes of new England head coach Eddie Jones' tenure, after suffering the serious injury in Saturday's 41-27 Premiership victory over Wasps.
Exeter Chiefs head coach Rob Baxter has confirmed Slade had "a pretty major operation" on Sunday.
"The reality is it is a decent injury, so you would normally talk around four months for an injury like this," said Baxter, who also confirmed flanker Dave Ewers will not feature again before January owing to knee ligament trouble.
"We are certainly not pencilling in any date for Henry's return because we know it is long-term.
"We will start talking about a return date in eight to 10 weeks' time when we know a bit more - it will take a bit of time though and a lengthy rehab process.
"He has had what all indications suggest was a successful operation.
"He has had a plate inserted into the lower part of his leg, he had to have some ligament repair and a bit of wire instead at the lower end of his leg too.
"It was a pretty major operation but certainly not one we don't expect him to make a full recovery from."
Exeter playmaker Slade forced his way into Stuart Lancaster's World Cup squad only to kick his heels on the sidelines until England had been eliminated at the group-stage hurdle.
The England Under-20s graduate then featured in the walkover 60-3 victory over Uruguay that had no bearing on the overall competition.
Slade has since been tipped to feature prominently in England's reshaping, starting with the forthcoming Six Nations, but must now spend that time fighting back from serious injury instead.
Exeter boss Baxter also confirmed fellow England hopeful Ewers would be joining Slade in the treatment room.
"Dave will be a little while, it is going to be a few weeks before we will see him," said Baxter.