Chris Wilder's men are level on points with Burton but sit in second thanks to their superior goal difference.
The two sides are unbeaten so far this term and a win for either could put them top, if leaders Chesterfield drop points against rock-bottom Accrington Stanley.
However, Paul Cook's men will be overwhelming favourites for the tie against his former employers, with the visitors having picked up just one point from their opening five fixtures.
Cook's side clinched top spot with a 2-0 win over Portsmouth last time out but he believes there are still improvements to be made.
"I never try and kid our fans and make out that everything’s great, we haven’t played well the last couple of games but we’ve got two fantastic results," he told the club's official website.
"We must work very hard in training, we must be bright with our passing, we must be more inventive and we must work harder to win games."
With just two points separating Oxford in second and Southend United in seventh, the four teams in the play-off spots will be aware of the importance of a win.
Fourth-place AFC Wimbledon travel to Bootham Crescent to face a York City side without a win since the opening day while, a place below, Exeter City travel to Dagenham and Redbridge.
Fleetwood Town will look to bounce back from their 2-0 defeat to Wimbledon when they welcome Torquay United as Southend seek to avoid three consecutive defeats against a buoyant Morecambe who have won their last two league matches.
Hartlepool United, fresh from their 5-0 Football League Trophy win over Bradford City on Tuesday, can pick up their first win of the season in the league against Wycombe Wanderers at Victoria Park.
Forward Andy Monkhouse believes his team-mates can bring their belief from the victory into the league, where they are yet to find the net this term.
"By the end (of the Bradford game) it could have even been more than five goals," he told the club's official website.
"Towards the end everyone wanted the ball, people were trying tricks, we were all running and tackling – I think the belief was there for all to see."
Northampton Town hover precariously above the drop zone, with just one win to their name this season, but Aidy Boothroyd's men can move clear of the bottom two when they host Scunthorpe United.
Cheltenham Town are in similar trouble at the bottom and will need to keep David Connolly quiet when they take on Portsmouth, with the 36-year-old having struck four times so far this season.
The two sides promoted from the Conference Premier last season, Newport County and Mansfield Town, meet for the first time in the league on Saturday, having made impressive starts to their domestic campaigns.
Both have lost just once in their five games and can move into the top seven with victory.
South west neighbours Plymouth Argyle and Bristol Rovers meet at Home Park while there is a Lancashire derby at Spotland as Rochdale host Bury.
