The former England striker has not yet had a scan on the injury, sustained form a reckless challenge from behind by Stoke's Ryan Shawcross in the 4-2 at the weekend.
Jeffers has had an x-ray on the ankle but because of swelling and blood within the joint, a full assessment can not be assessed although a specialist has said he has ruptured ligaments and will miss three months.
Scunthorpe United come to town tonight as Brian Laws faces his old club for the first time with Deon Burton and Marcus Tudgay expected to start in attack.
Steve Watson and Frank Simek remain doubtful along with Wade Small.
Graham Kavanagh and Michael Johnson are set to play their penultimate games for the club before returning to Sunderland and Derby respectively although it is hoped that the duo will stay on loan at Hillsborough.
A big welcome for former Owls keeper Kevin Pressman is expected - the Hillsborough legend is now goalkeeping coach at Glanford Park and returns to S6 for the first time tonight.