Grant, who has started every game so far in the ITM Cup for Otago, picked up a bang on his quad in the first half of the match against Manawatu last Friday and did not come back out for the second half.
Otago coach Tony Brown said Grant was still feeling the impact of his leg injury and he had endured a big workload this season and was in need of a rest.
Brown said he had full faith in all his loose forwards. Liam Coltman will skipper the side.
TJ Ioane, who has been coming off the bench for the majority of the season, will start the game at No 8, replacing Grant. Ioane's place on the bench is taken by Lee Allan.
Apart from Grant being rested, Brown has stuck with all but the same team which beat Manawatu in a high-scoring encounter at Forsyth Barr Stadium last Friday night.
Lock Tom Donnelly comes back into the team after he was a late scratching last week because of a stomach bug.
Prop Scott Manson is free to start after he was given an off-field yellow card for an incident in the match against Manawatu. Manson was cited for stamping on Manawatu prop Chris Eves.
Judicial officer Roger Drummond found while there was foul play from Manson and the citing was upheld, it was at the low end, and a period of suspension would outweigh the level of offending. The off-field yellow card allows him to play but will be on his record for the rest of the season.
Brown said there was not much in the incident but it always sharpened up the player affected.
Drummond also took into account the player's good record and his conduct at the hearing.
Otago will be seeking to push on from its win over Manawatu and knows it must improve its defence against Southland.
Southland has named an unchanged side to play Otago, fresh off a come-from-behind victory over North Harbour.
As well as being prop and skipper Jamie Mackintosh's 100th game, the match will be the 99th for Southland for veteran hooker David Hall.
Scott Eade will continue at halfback for the Stags.
Southland sits just one point ahead of Otago on the ITM Cup championship table.
Otago holds the Donald Stuart Memorial Trophy.