Luke O'Brien could makes his Exeter debut.
The full-back arrived at St James' Park from Bradford on transfer deadline day but was not part of the matchday squad that lost 2-0 at Bournemouth on Tuesday.
O'Brien will compete with Billy Jones for the left-back position, and manager Paul Tisdale otherwise has a fully-fit squad at his disposal.
After extending his loan from Reading by a further month, Jake Taylor could return to the starting line-up in attack after coming off the bench against the Cherries in midweek, while Liam Sercombe has recovered from injury.
Midfielder Sercombe could also come back into the side in place of Scot Bennett, as Exeter host the Owls chasing their first victory - and their first goal - in five League One matches.
Sheffield Wednesday manager Gary Megson must decide whether to recall defender Miguel Llera or retain skipper Rob Jones at the heart of defence.
Jones returned for the midweek FA Cup defeat to Blackpool after missing the previous four games due to an ankle injury while on-loan Llera was ineligible to play against his parent club.
Megson made seven changes for the fourth-round replay on Tuesday night and is expected to revert back to something similar to the side that started in last week's league match against Yeovil.
John Bostock, on loan from Tottenham, is likely to be recalled, as is fellow midfielder David Prutton, while winger Jermaine Johnson, who has scored three goals in his last five games, will return after being rested.
Strikers Gary Madine and Chris O'Grady are also likely to return to the starting XI as the Owls bid to extend their unbeaten away record in the league to four matches.