Reds head coach Nick Stiles has named his side to play the Lions at Ellis Park in Johannesburg, making two changes to his starting line-up.
In total there are three changes to the 23 which lost to the Crusaders last week.
Hooker Andrew Ready has gained his first start of the season, coming into the number two jersey, with Stephen Moore shifting to the bench.
Lock Kane Douglas also returns to the starting side after Izack Rodda was unable to train fully due to a head knock against the Crusaders.
That change has also allowed Lukhan Tui to come into the matchday 23 for the first time this season as a reserve.
Reds: 15 Karmichael Hunt, 14 Izaia Perese, 13 Samu Kerevi, 12 Duncan Paia’aua, 11 Eto Nabuli, 10 Quade Cooper, 9 Nick Frisby, 8 Scott Higginbotham, 7 George Smith, 6 Hendrik Tui, 5 Kane Douglas, 4 Rob Simmons, 3 Sam Talakai, 2 Andrew Ready, 1 James Slipper (c)
Replacements: 16 Stephen Moore, 17 Markus Vanzati, 18 Taniela Tupou, 19 Lukhan Tui, 20 Adam Korczyk, 21 James Tuttle, 22 Jake McIntyre, 23 Chris Kuridrani
Date: Saturday, March 18
Venue: Emirates Airline Park, Johannesburg
Kick-off: 17:15 local (15:15 GMT)
Referee: Mike Fraser (New Zealand)
Assistant Referees: Jamie Nutbrown (New Zealand), Stuart Berry (South Africa)
TMO: Willie Vos (South Africa)