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Cape Town - Derby rivals Mamelodi Sundowns and SuperSport United will battle at the Lucas Moripe Stadium.
Read: 'Downs hopeful of injury returns
Sundowns have put together a seven-game unbeaten run but played to a fourth successive draw when they were held 1-1 by Kaizer Chiefs in their last outing.
The Tshwane side has claimed just six points from five home matches this season.
Their next three league opponents are Free State Stars (home), Orlando Pirates and University of Pretoria (both away).
The Brazilians are placed seventh on the PSL log with 17 points from 11 matches.
SuperSport suffered their sixth defeat of the season when they were beaten 2-1 at home by Orlando Pirates in their last league outing.
The Tshwane side has claimed six points from four away matches this season.
Their next three league opponents are Ajax Cape Town (away), Polokwane City (home) and Bidvest Wits (away).
Matsatsantsa are placed 10th on the Absa Premiership log with 15 points from 11 matches.
In head-to-head stats, Sundowns and SuperSport have met in 46 league matches since 1990.
The Brazilians have 21 wins compared to 14 for Matsatsantsa, while 11 matches have been drawn.
Sundowns have won nine of their 23 home matches against United, suffering nine defeats in the process.
Last season the Brazilians took four points off Matsatsantsa, drawing 1-1 away before winning the return game 3-0 at home.
Kick-off is at 19:30 on Wednesday, December 3.
