City are top of the PSL log with 46 points, two clear of Downs who have two games in hand on their title rivals.
The Urban Warriors are desperate to salvage their season and stop from falling further than their 10th-place spot in the standings.
And Stanley Menzo and his team will be looking for any result from the Loftus clash to get their top-eight hopes back on track.
Sundowns are favourite to run away with the points, despite Ajax getting the better of them at the end of last year.
But with Downs winning three games on the trot, including a 5-0 win over rivals SuperSport, Ajax are hoping for the best.
Menzo says: “If that happens [we get a good result in Pretoria], I am sure we can then start to look up the log if possible.
“But I still believe – look the way we played last Saturday [draw with Golden Arrows].
“It was incredible that we failed to win against a team who has a good home record. We have to keep that spirit, we have to keep to that way of playing and I am sure we can make it very difficult for Sundowns and that we will win more games.
“But again, it is more a mental thing, do we have the belief in ourselves that we can do it?
“Yes, we are not one of the big teams, but we can do much better.”