Ramiro Funes Mori is unlikely to play again this season due to a knee injury in another huge blow for Everton, who have also lost Seamus Coleman to a broken leg.
Funes Mori sustained a torn meniscus when playing in Argentina's 2-0 defeat in Bolivia on Tuesday, meaning he had to be replaced in the first half.
Everton are not optimistic over the chances of the defender returning before the end of the campaign after carrying out initial tests upon his return to the club.
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"Funes Mori will have a surgical opinion next week but the initial diagnosis suggests the 26-year-old is likely to be out of action for the rest of the campaign," read Everton's statement.
Centre-back Funes Mori has played 23 Premier League matches this season, with the blow coming at a crucial time in Everton's season.
They have nine Premier League matches left in a bid to clinch a Champions League spot, with crucial matches against top-four rivals Liverpool and Manchester United to be played inside the next week.
Funes Mori's injury comes after starting right-back Coleman suffered a double leg fracture while playing for Republic of Ireland against Wales during the same international break.
Everton also without Yannick Bolasie and Muhamed Besic with long-term knee injuries, although Morgan Schneiderlin (calf) is closing in on a return to full fitness.