England centre Henry Slade will miss the start of the Six Nations because of the ankle injury sustained on Gallagher Premiership duty for Exeter.
Slade was forced off in the first-half of last Saturday's 31-22 victory over Leicester after damaging his right ankle and has been ruled out for six to eight weeks.
England open their Six Nations campaign against France on February 2 but Eddie Jones must now plan for the trip to Paris without a key component of his backline.
"Henry has a small fracture to his ankle around the site of the plate he had put in a couple of seasons ago when he fractured it at Wasps," Exeter boss Rob Baxter said.
"The prognosis of anything like that is six to eight weeks of healing time. There's no information at this stage that says it will be quicker or slower than six to eight weeks.
"It's not for me to say for which game exactly he'll be back because things can shorten up considerably towards the end of rehab time or they can relapse at the end, so it's impossible for me to say."
Slade has been a regular for England since cementing his place in the team during the 2018 tour to South Africa and was involved in the World Cup after recovering from a knee problem.