England lock Maro Itoje fractured his jaw playing for Saracens against Harlequins on Sunday, a scan has shown.
The 23-year-old, who collided with Mike Brown, will visit a specialist this week to determine when he can return.
England begin the defence of their Six Nations title in less than nine weeks, away to Italy on Sunday, 4 February.
Itoje, who has 14 caps, started every match as Eddie Jones' side won the 2017 title, but only played in two autumn Tests as his playing time was managed.
After a heavy schedule that included starring for the Lions as they drew their series 1-1 away to New Zealand in the summer, the versatile forward was rested for England's opening fixture against Argentina, came off the bench against Australia and started the victory over Samoa.
He was forced off in the 48th minute of Saracens' 20-19 Premiership defeat by Quins at The Stoop.
Sarries play Clermont home and away in the European Champions Cup over the next couple of weekends, before visiting Leicester Tigers in the Premiership on 24 December.
BBC Radio 5 live rugby union reporter Chris Jones
"It's somewhat ironic that, after being rested by England this autumn to protect his welfare, Itoje suffered this setback on his immediate return to club duty.
"While Saracens have yet to put a date on his return, it's fair to say an injury like this will need a minimum recovery time of six weeks - and anything longer would threaten Itoje's involvement in the start of the Six Nations.
"But the more immediate repercussions will be felt by Saracens, who are on a rare poor run of form, and will be without the world player of the year nominee for the crucial upcoming fixtures against Clermont in Europe."
Source: BBC Rugby Union News