Everton manager David Moyes said Jagielka, who has a history of knee problems, had suffered medial ligament damage in the midweek defeat to Bolton Wanderers and was now not likely to return to action until mid-February.
"Jags has got medial ligament damage," said Moyes, adding he would be out for "up to six weeks."
"Losing Jagielka is an incredibly big thing for us because the one thing about the team at the moment is they have been very strong defensively in the main. To lose him is a massive blow to us because he is an integral part of the defence and very important to us."
Jagielka, 29, spent nearly a year on the sidelines in 2009 after a different knee injury.