James Simpson-Daniel will undergo surgery to correct ankle ligament damage sustained during Gloucester Rugby's Heineken Cup defeat against Cardiff Blues last Sunday.
The England winger had an MRI scan and, following consultation with a foot and ankle specialist, will be out of action for 12 weeks.
The 2008 Premiership player of the year sustained an isolated rupture in his right ankle at the Millennium Stadium and will miss all the remaining four Heineken Cup Pool stage matches with the "Cherry and Whites" and England's autumn Tests.
Gloucester's head coach Dean Ryan said: "To lose a player of James' quality is obviously a massive blow to us.
"He is an outstanding player and central to our attacking threat. Considering the other injuries we have across our backline this could not have come at a worse time for us."