The visitors, meanwhile, will have the chance to claim consecutive victories following a 3-1 win over Accrington Stanley.
Match preview
Exeter went four games without defeat before they faced Portsmouth on Saturday, and although they were also looking to record a third consecutive away victory, two second half goals condemned them to a 2-0 defeat.
The result saw the Grecians slip down from 10th to 12th position on goal difference, leaving them eight points adrift of the top six, having played a game more than Tuesday's opponents who sit in the final playoff place.
While a top six finish may prove difficult, a win over Barnsley would certainly enhance their hopes of mounting a playoff push, however, that would require Exeter to end their four-game winless home run.
Converting home draws into victories has been their real problem of late, with their last three matches at St James Park finishing all square.
Exeter will at least take confidence from the 2-0 away victory they picked up against Barnsley in the reverse fixture in October.
Barnsley lost three straight competitive games by a combined 8-0 scoreline before they played host to Accrington Stanley at the weekend.
However, the Tykes wasted little time in bringing their mini goalscoring drought to an end, finding the net on three occasions in the opening 20 minutes, thank to efforts from James Norwood, Jack Aitchison and Jordan Williams.
A 94th-minute consolation goal from Accrington's Tommy Leigh denied Barnsley the clean sheet, but that would have done little to dampen the mood, as Barnsley ended the weekend with a five-point cushion over the sides just outside the playoff places.
The Tykes will now look to record consecutive victories, and although they have only taken one point from their last two away league games, they have been a resolute force on their travels.
Only two teams in the third tier have conceded fewer away goals than the 10 Barnsley have shipped, while they have only let in more than one goal in one of their last nine league matches on the road, which was incidentally a 2-0 defeat to Charlton Athletic in their most recent away match.
Exeter City League One form:
L
D
W
W
D
L
Barnsley League One form:
W
D
W
L
L
W
Barnsley form (all competitions):
D
W
L
L
L
W
Team News
Exeter recently recalled Josh Coley from a loan spell with Harrogate, but he is yet to feature since his return due to injury, and he is set to miss Tuesday's game alongside Kyle Taylor, who is also sidelined.
After dropping out of the side, Aaron Collins came off the bench at half time against Portsmouth, and he is expected to return to the starting XI in midweek.
Newcastle United loanee Joe White is set to retain his place in the lineup after being given his first start for the club on Saturday.
As for the visitors, they are unable to call upon the services of Robbie Cundy and Josh Benson due to knee and hamstring injuries respectively.
Luke Thomas and Slobodan Tedic also remained sidelined, with the pair expected to return to training at the end of the month or early February.
After recently joining on loan from Burnley, Bobby Thomas made his Barnsley debut on Saturday, and he is expected to feature in midweek, with Duff set to name an unchanged lineup.
Exeter City possible starting lineup:
Blackman; Sweeney, Diabate, Hartridge; Caprice, Collins, Kite, Key; White; Brown, Nombe
Barnsley possible starting lineup:
Collins; B. Thomas, Andersen, Kitching; Williams, Connell, Kane, Phillips, Cadden; Norwood, Aitchison