Everton midfielders Abdoulaye Doucoure and Fabian Delph are each expected to be out for a minimum of four weeks after sustaining injuries.
Doucoure was forced off in the 65th minute of Saturday's 1-0 Premier League defeat by Aston Villa at Goodison Park due to a groin problem.
Subsequent tests have revealed the 29-year-old requires a period of rehabilitation under the care of Everton's medical staff.
It is another setback for Doucoure, who missed four consecutive league games earlier this season due to a foot issue. He has scored two goals and registered four assists in 18 matches in all competitions.
Meanwhile, Delph sustained a thigh injury during a training session this week and is now undergoing treatment with the club's medical team.
The 32-year-old has not played for the club since December 12.
With Tom Davies also out for an extended period of time, Everton interim boss Duncan Ferguson has few fit midfielders to call upon.
Allan, Andre Gomes, and Jean-Philippe Gbamin are available, as well as 18-year-old Tyler Onyango.
Forwards Dominic Calvert-Lewin and Richarlison, as well as defender Yerry Mina, have also struggled with fitness this season but all three played the full 90 minutes against Aston Villa on Saturday.
Everton - who are continuing their search for a permanent manager - are four points clear of the relegation zone in 16th place ahead of important matches against Newcastle, Leeds and Southampton.
What games could Doucoure and Delph miss?
- Saturday, February 5: Everton vs Brentford - FA Cup, kick-off 3pm
- Tuesday, February 8: Newcastle vs Everton - Premier League, kick-off 7.45pm
- Saturday, February 12: Everton vs Leeds - Premier League, kick-off 3pm
- Saturday, February 19: Southampton vs Everton - Premier League, kick-off 3pm
Pereira: 'It's time for Everton decisions' | 'Critics don't know me'
Everton managerial candidate Vitor Pereira says "it is a time for decisions" as he waits to hear whether he will be handed the role as Rafael Benitez's successor.
Pereira is understood to be the favourite to take over at Goodison Park and, in an exclusive interview with Sky Sports News, the 53-year-old revealed he had received "good feedback" after having talks with Everton owner Farhad Moshiri and chairman Bill Kenwright.
Pereira also offered details of his plan to turn around Everton's fortunes, saying his first task would be to install the "organisation" that has been lacking amid the club's fall to 16th in the Premier League.
"I had a few interviews - not just one," explained Pereira. "More than one interview with different people at the club.
"We discussed everything. I discussed with different people in the club and on the board.
"I gave them my point of view about the club and what I think about the team, because they asked me to come, Moshiri and Bill Kenwright and other people in the club."
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