Liam Sercombe and Alan Gow are set to return to Paul Tisdale's Exeter starting XI.
The duo returned to the bench for last weekend's defeat to Northampton after recovering from ankle injuries.
But Tisdale is set to ring the changes following successive losses and both are expected to be handed a starting role.
Striker Gow did replace Kevin Amankwaah at the break in that fixture and he is now likely to drop to the bench with Steve Tully moving over to right-back.
Returning midfielder Sercombe insists he is ready to get the Grecians' season back on track after declaring himself fully fit.
"He (manager Paul Tisdale) has brought me back in slowly, but I felt great on Saturday and now I am ready to start a match," he told the Western Morning News.
"I am confident I will start the game on Saturday and push the team forward. The manager might decide to change a couple of tactical things on Saturday and try something new."
Chesterfield are boosted by the return of Marc Richards and Nathan Smith.
Richards has been absent since he was carried from the field on a stretcher after suffering an ankle injury during the closing stages of the thrilling 4-3 home win over Accrington on September 18.
The 30-year-old striker, who scored his first goal for the Spireites following his summer arrival from rivals Port Vale in that game against Stanley, has trained this week and will travel to Devon.
Smith, sidelined since the end of August with his ankle injury, played the full 90 minutes of a reserve team game on Wednesday night and the left-back will also be in the squad.
Sam Togwell is nursing a bruised knee following last weekend's home defeat to Dagenham & Redbridge and he will undergo a late fitness test.
Elsewhere in midfield, Danny Whitaker is expected to be fit after a groin problem but Mark Allott (hamstring) will remain out.