Rodwell was out for 11 weeks earlier this season after damaging his ankle ligaments in August, and has been limited to 17 appearances this term.
His latest lay-off means he will return for the Premier League clash at home to Fulham on 19 March at the earliest.
Rodwell, who has previously captained England's under-16 and under-18 sides, was part of the under-21 team that lost to Germany in the final of the European Championship in 2009.
Rodwell, who made his Everton debut at the age of 16 in December 2007, had started the side's last three matches but will now miss league matches against Bolton, Sunderland, Newcastle and Birmingham and the FA Cup fourth-round replay against Chelsea.
Several of his international team-mates withdrew from the U21 friendly in Empoli with minor knocks.
Eight players - including Liverpool's Martin Kelly, Manchester United's Chris Smalling and Manchester City's Micah Richards - pulled out of manager Stuart Pearce's squad over the weekend.
Rodwell's impressive form last season, during which he scored four goals in 36 appearances for the club, sparked speculation that a ?15m bid from Manchester United was imminent.
But the Southport-born star reaffirmed his commitment to the club by signing a new five-year deal at Goodison Park last May.
Source: BBC Sport
Source: BBC Sport