Saturday's action kicks off at the Cape Town Stadium where rivals Cape Town City and Ajax Cape Town lock horns for three priceless PSL points, as well as pride and bragging rights.
Later in the day, Absa Premiership leaders Sundowns welcome Platinum Stars while Pirates are also at home, against Polokwane City.
On Sunday, Kaizer Chiefs face a tricky trip to Baroka FC in the only PSL-focused match of the day, with European action seeing Real Madrid take on Deportivo La Coruna while Barcelona are away at Real Betis.
There's also action from France where Neymar's Paris Saint-Germain travel to Lyon while in England, Southampton and Tottenham do battle in the day's only Premier League fixture.
KickOff Predictor - Round 64 fixtures:
Saturday 20 January
Brighton v Chelsea
Cape Town City v Ajax Cape Town
Mamelodi Sundowns v Platinum Stars
Orlando Pirates v Polokwane City
Manchester City v Newcastle
Sunday 21 January
Baroka FC v Kaizer Chiefs
Real Madrid v Deportivo
Southampton v Tottenham
Real Betis v Barcelona
Lyon v Paris Saint-Germain