England fly-half Marcus Smith (24) will miss their Six Nations opener against Italy on Saturday after limping off during a training session, assistant coach Kevin Sinfield said on Tuesday.
"(Marcus) won't make this weekend, sadly," Sinfield told British media.
"We got the scan report through but we are waiting to understand exactly what that means for us moving forward. He's not fit for this weekend."
With fly-half Owen Farrell ineligible for selection after signing with French club Racing 92, Smith's absence will "definitely be a blow," England attack coach Richard Wigglesworth told British media.
England are already without centres Ollie Lawrence and Oscar Beard and hooker Luke Cowan-Dickie for the match in Rome on Saturday.
Coach Steve Borthwick could turn to George Ford at number 10, with the uncapped Fin Smith another option.
Borthwick is scheduled to announce his starting line-up on Thursday.