Spireites manager Paul Cook could welcome back Tommy Lee and Marc Richards.
Highly-rated goalkeeper Lee (shoulder) and striker Richards (hamstring) have been sidelined since the start of September and are "very close" to making their comebacks.
When asked if the duo will be fit for Saturday, Cook, who has also been without on-loan defender Liam Cooper, midfielder Mark Allott (hamstring) and striker Luis Boa Morte (groin) in recent weeks, said: "Watch this space.
"We have to be careful what we say about injuries as last week we said Tommy Lee would be ready, so then all the fans get excited, but he wasn't.
"We obviously want everyone back as soon as possible. But what I will say is that we have had a number of players who have been out injured who are now training with the first team and they are very close."
Cook hinted that Brennan Dickenson would make his full debut against the Us. The teenage forward, who joined Chesterfield on loan from Brighton last week, marked his first appearance for the club from the bench with a goal during the 3-2 defeat at Bristol Rovers.
Alfie Potter has given Oxford boss Chris Wilder a boost ahead of their trip to Derbyshire by returning to training after a hamstring injury.
The 23-year-old, who has scored five times this season, missed the defeat at Dagenham and the draw with Torquay last weekend but is expected to make the trip north after making a full recovery.
Wilder handed defender Liam Davis his first start of the season against the Gulls after the full-back had been missing since May through injury.
Until their recent blip Oxford had only lost two of their previous eight games, a spell which included a 5-0 thrashing of Accrington and a 3-1 win away to Wycombe, but one point from their last two games means they are 17th in the standings.