Talbot missed the 2-0 home win over Bristol Rovers last Saturday with a virus.
The 26-year-old could be considered for a spot at full-back or on the wing, meaning Richard Brindley and Conor Townsend are the players most under threat in the starting line-up.
Tendayi Darikwa continued his return to fitness following a double hernia operation with a run-out for the reserves this week and the winger is also back in contention for a starting role.
Oxford include three former Spireites among their ranks in Deane Smalley, Andy Whing and Peter Leven, although the latter is out with a knee injury.
Chesterfield really need to win at the Kassam Stadium to keep their fading play-off hopes alive.