Rea had to be substituted in the first half of Saturday's home win over Burton, and isn't fit to take his place in the team for the Boxing Day game at Scunthorpe United.
Grant, who replaced him in the 2-0 win over the Brewers at Kenilworth Road, comes in for his first start since the Accrington Stanley game on October 23.
Alan McCormack comes onto the bench along with Lloyd Jones, who replaces Dan Potts, as the second-placed Town seek a seventh straight league victory at the club who sit in 21st place, one inside the relegation zone, at kick-off.
In Rea's absence, and with club captain Alan Sheehan on the bench, Sonny Bradley will skipper the side.
TOWN: Shea, Stacey, Pearson, Bradley (c), Justin, Mpanzu, Shinnie, Grant, Lee, Collins, Cornick. Subs: McCormack, Berry, Hylton, LuaLua, Jones, Sheehan, Stech
SCUNTHORPE: Alnwick, Borthwick-Jackson, Ojo, Perch, Novak, Thomas, Ben El-Mhanni, Goode, Sutton, McArdle (c), Wootton. Subs: Flatt, Horsfield, Ugbo, Humphrys, Dales, Lewis.
REFEREE: Martin Coy