Heskey suffered an ankle injury after coming on as a substitute during the second half of Saturday's 2-0 home success over Portsmouth.
Martin O'Neill is set to make changes and midfielder Nigel Reo-Coker could be involved after being axed for the Pompey match following a training ground spat with the Villa manager.
The likes of Nicky Shorey, Craig Gardner, Habib Beye, Fabian Delph, Brad Guzan and Nathan Delfouneso may also get a starting spot.
Cardiff midfielder Stephen McPhail will miss out.
McPhail was sent off in last week's win over Reading and despite an appeal the decision was upheld by the FA of Wales.
The 29-year-old missed the weekend loss against QPR and will serve the second game of a three-match ban against Villa.
Dave Jones is set to ring the changes and give his fringe players a run-out, with Peter Enckelman, Gabor Gyepes and Tony Capaldi expected to feature.
Adam Matthews could make a return to the squad if he recovers from a groin problem in time, and fit-again Riccy Scimeca will be pressing for a start against his old club after his return at the the weekend.
Striker Ross McCormack has suffered a setback in his recovery from a hamstring injury and will miss out, meaning youngster Josh Magennis could come into the attack to partner Jay Bothroyd or Michael Chopra.
Aston Villa (from): Friedel, Guzan, Cuellar, Beye, Clark, Dunne, Collins, Lowry, Warnock, Shorey, Milner, Gardner, Petrov, Delph, Sidwell, Reo-Coker, A. Young, Carew, Agbonlahor, Delfouneso, Heskey.