Lars Jacobsen will be out for up to four months with a dislocated shoulder.
The Dane picked up the injury while playing for Denmark against Portugal in midweek.
Consultation with a specialist has revealed the defender will require surgery, keeping him out until December at the earliest.
"We didn't get good news on Lars," manager David Moyes told the club's official website. "He will need an operation that will keep him out for three or four months.
few injuries
"It is a blow to the boy, and we have had a few injuries - which is part of football. He was just beginning to settle in and we were looking forward to using him."
The former Nurnberg and FC Copenhagen defender has yet to make his debut for the Toffees following his free-transfer signing this summer, although he had been pencilled in to do so against Stoke City this weekend.
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