Roberto Martinez says Antolin Alcaraz is set to be out for a "long time" after suffering a shoulder injury against Swansea.
The Paraguayan sustained the injury in a challenge with Wilfried Bony 32 minutes into the 0-0 draw and had to be replaced by Muhamed Besic.
Alcaraz was taken to hospital for scans and although the club have yet to reach an exact diagnosis, Martinez concedes the 32-year-old may be out for a while.
"Antolin has damaged a joint in his shoulder. We're going to assess him tonight and tomorrow morning but it seems he's going to be out for a long spell.
"It's a real shame because he had to work really hard to get back to full fitness and perform. He fought hard for his place and was in a good moment. It was an accident and you don't usually get those sort of injuries in football.
"But we'll help him through it and hope he can come back before the second half of the campaign."
It is the latest in a long line of injuries for Alcaraz, who made just seven appearances last season and was playing just his fourth game of this campaign.
With his contract up at the end of next season you have to wonder whether Martinez will offer the defender a new deal, unless he can string a run of games together during the second half of the season.
His absence further compounds Everton's defensive worries, with John Stones already sidelined with an ankle ligament injury until at least December.
Martinez, though, insists he has enough depth in his squad to cope with the absence of both players.
"Sylvain Distin has been working really well and he played very well in the Europa League in Lille.
"You don't want to lose any player, but we knew we were going to get injuries and suspensions and that's why we've got a stronger and larger squad [than last year].
"Sylvain has done well, so has Tyias Browning, who can play as centre-half, and we also have young Brendan Galloway. "We've got opportunities and options throughout the squad."