Roberto Martinez fears he could be without Ross Barkley for up to five months.
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The England midfielder damaged the medial ligament in his right knee in training one day before their opening Barclays Premier League match against Leicester, which ended in a 2-2 draw.
Everton will have to wait to find out the full extent of the damage but Martinez knows he could be without one of his key players for a large chunk of the season.
The Toffees boss said: "He had a scan but it was a bit difficult to determine the extent. With the swelling we don't really know how bad the injury is.
"We know it's a partial tear but that could be anything between seven weeks and I've seen injuries like that that take four or five months.
"Ross Barkley is a phenomenal footballer and we're going to miss him, there's no doubt about it. He was so sharp in pre-season, I thought he came back with a different approach.
"He was very unfortunate to (sustain the injury) through an innocuous challenge in training and now he's going to be out for a long, long time.
"The squad should be big enough to be able to cope with losing a player and be able to perform well, but it's a disappointing moment when Ross Barkley was going to have a really big start to the season.
"Now it's coping with the frustration and allowing him to come back when he's fully fit and ready for whatever's left in the season."
The injury is also a blow to England, with Barkley looking certain to miss the Euro 2016 qualifiers against Switzerland, San Marino and Estonia at the very least.
Barkley is no stranger to serious injury having broken his leg in three places on England Under-19 duty in 2010.
Martinez backed the 20-year-old to cope with his latest setback, saying: "He's a very mature boy.
"He was very disappointed because he was looking forward to the start of the season and he put a lot of extra work in because he came back from the World Cup with a real desire to start the season well.
"He's been through periods of bad adversity before and he knows how to cope with that.
"As a football club we're going to be with him and make sure that he's not suffering too much while he's away. I think the ones that are going to suffer is us."
To add to Martinez's disappointment, Everton were unable to secure three points at the King Power Stadium after twice taking the lead.
Aiden McGeady's exquisite curling finish put the visitors ahead in the 20th minute but Championship winners Leicester hit back inside two minutes through record signing Leonardo Ulloa.
Steven Naismith struck a firm shot in off the bar just before half-time and that looked set to be the winning goal until substitute Chris Wood tucked away the equaliser in the 86th minute.
Leicester were prepared to sell Wood to Wolves before the deal fell through but the striker proved his worth with the goal eight minutes after coming on as a substitute.
Leicester boss Nigel Pearson, who confirmed he is still pursuing former Argentina international Esteban Cambiasso, said of Wood: "He's staying here.
"I've spoken to him on a couple of occasions this week and he's very happy to stay here and fight for his place. I'm pleased to have him here and for him to respond in the way he did speaks volumes for his ability to put things behind him and carry on.
"It can be unsettling for any individual to be involved in speculation surrounding their future, especially at his age."
Leicester are back in the Premier League for the first time in a decade and Pearson had no doubt they deserved their point.
"It's nice to get something out of the game," he said. "I'm disappointed that we've been unable to win.
"We went behind twice, and from my perspective there was an element of misfortune about both goals, not doubting the quality of the finishes. The first finish was unbelievable.
"It would have been easy, especially with the second goal, to think things weren't going our way, but I'm very pleased with how we responded and in the second half we looked pretty dangerous."
Leicester were the side doing all of the pressing in the second half, with Everton only looking a threat after Wood had equalised.
Martinez bemoaned his side's lack of urgency, saying: "We should have won but it's only us to blame.
"I thought the first half we did everything we had to do, we controlled the environment. We did the hardest thing, which is get yourself in front twice.
"The first goal we conceded was very unfortunate, just a rebound from a corner, and the second one we probably got too relaxed.
"If I've got a criticism from our point of view it's probably we should have gone for that third goal with a bit more brightness rather than just controlling the game."