The former England striker Jeffers started in the defeat to Ipswich but then limped out of the home loss to Wolves after only 20 minutes with a calf problem - and has been out ever since.
He will line up in attack with Akpo Sodje - who is also looking to gain much-needed match fitness as he bids for his first Owls starting spot.
Should Jeffers come through the game unscathed, he is a near certainty to be part of the squad which travels to Deepdale on Saturday in which is turning out to be a much-win game already with The Owls pointless from four games.
Assistant manager Russ Wilcox is looking to get at least a full half out of Jeffers as well as fielding Small after the winger recovered from a knee injury.
Small is being tipped to take over Jermaine Johnson's right-wing spot on Saturday as the Jamaican has run hot and cold so far this season while the former MK Dons man started the season in fine form before being struck down by the Middlewood injury jinx.
Etienne Esajas will start in a strong team which also features Kenny Lunt, Yoann Folly, Mark Beevers and Richard Hinds.