The Brazilians cruised through their Second preliminary round tie with a 7-1 aggregate victory over Nigeria's Remo Stars.
Lupopo, meanwhile, overcame Al Merrikh 1-0 in their First round clash before sensationally dumping Orlando Pirates out of the competition in the Second round, following a penalty shootout, after a 3-3 draw.
The two sides were paired together in Group C alongside Al-Hilal and MC Alger.
Sundowns head into the group stage with a singular focus, to improve on last season's Champions League campaign, where they ended as runner's up to Egypt's Pyramids FC.
Speaking ahead of the weekend's encounter, Brazilians boss Miguel Cardoso explained his intention to fight for every trophy on offer.
He said on KickOff, ahead of the tie: "I think that we need to have a clear focus on winning competitions.
"It is not only on winning the Champions League."
Cardoso added though that Sundowns don't have a right to win the Champions League and will not make it an obsession to add a second star.
"I know that throughout the competition, everyone will take out the pressure on their teams by saying that we are the ones that should win, and they are the ones that are just participating. It has started very quickly this kind of speech," he explained.
"The Champions League is a trophy that the club seeks for 10 years. Unfortunately, last year we were unable to bring this trophy to South Africa general but mostly to our fans and our club.
"As you can imagine, myself I’m even in a worse situation because for two years in a row, I am there and I could not win. But that will take nothing from us but give us the energy to seek this objective and understand that in the end, it will be by details that the team will win."
Lupopo coach Guy Bukasa will not be on the bench for his team as he serves a six-match ban, starting with this game.
They will also be without controversial defender Dieumerci Mukoko Amale, who is serving a two-match suspension.
Sundowns have Iqraam Rayners available again after he returned to competitive action recently following an extended lay-off.
Saint-Eloi Lupopo assistant coach Yassine Salmi believes the team's growth and tactical maturity will be crucial as they prepare for another major test against Mamelodi Sundowns.
Chilean midfielder Marcelo Allende admits it's crucial for Mamelodi Sundowns to win their opening CAF Champions League group stage clash.
FC Saint-Eloi Lupopo will play their CAF Champions League match against Mamelodi Sundowns without suspended defender Dieumerci Mukoko Amale.
Mamelodi Sundowns midfielder Neo Maema has revealed that his decision to join Simba SC in Tanzania was driven by a desire for a fresh start outside South Africa.
