Tony Pulis is yet to pick up his first win as Wednesday manager, while The Tykes are enjoying a decent start to the campaign, sitting 10 points clear of the relegation places.
The Owls were hit with a 12-point deficit at the start of the season - which has since been reduced to six points - for breaching spending rules.
That deduction has left the South Yorkshire side rooted to the foot of the second-tier four points from safety.
Garry Monk was given the axe after a poor run of form left Wednesday with just three wins from their opening 11 league matches.
However, Pulis has been unable to turn things around at Hillsborough and is without a win in his first six games at the helm. The former Stoke City and Middlesbrough boss will be hoping he can inspire a change in fortunes sooner rather than later.
Valerien Ismael's men come into Saturday's clash in contrasting form, having picked up two wins in their last three outings.
Barnsley have yo-yoed between the Championship and League One in recent seasons, but their great escape in 2019-20 has given them a good platform to try and establish themselves in the second tier.
The 2-1 win over Wycombe Wanderers in midweek elevated them to 16th position in the table, a place Ismael will be looking to hang onto when they take on a Wednesday side short on confidence and form.
Barnsley do not usually fare too well against their more affluent neighbours and will see this as a great opportunity to get a rare victory over their county rivals.
Sheffield Wednesday Championship form: LDDDLL
Barnsley Championship form: WLLWLW
Pulis will not have the option to call upon experienced goalkeeper Keiren Westwood, who remains sidelined with a groin injury.
Nineteen-year-old defender Liam Shaw is serving the last of his three-match ban following a straight red card against Reading at the start of the month.
Forward Cauley Woodrow will be looking to continue his rich vein of form in front of goal after scoring twice in his last three appearances.
Sheffield Wednesday possible starting lineup:
Wildsmith; Iorfa, Lees, Borner, Odubajo; Harris, Paterson, Luongo, Bannan, Reach; Windass
Barnsley possible starting lineup:
Walton; Sollbauer, Halme, Andersen; Brittain, James, Mowatt, Styles; Chaplin, Thomas; Woodrow
We say: Sheffield Wednesday 1-1 Barnsley
Although Sheffield Wednesday are in a real rut, their home form has been a slight saving grace. They are unbeaten in their last four matches at Hillsborough and they should have enough to hold out for a draw against a buoyant Barnsley.