Mosimane's men are under some pressure heading into their second Group C match with Guinea's Horoya in Conakry (18h00 kick-off).
Sundowns rescheduled the game, which was initially set for last week, to accommodate the Nelson Mandela Centenary Cup clash with Spanish giants Barcelona at FNB Stadium on Wednesday.
Masandawana can ill afford to lose this game after dropping points against reigning champions Wydad Casablanca of Morocco in their group opener earlier this month, being held to a 1-1 draw in Tshwane. On the same day Horoya beat AS Togo-Port 2-1 in Lome.
Wydad, who replaced Downs as African champions last year, head the group with four points after beating Horoya 3-0 in their second pool contest.
"Wydad went and won 3-0 if I'm not mistaken against the Togolese side, so we have to try and win away in Guinea, Conakry to catch up," Mosimane said.
"Hopefully we win and be joint-leaders with Wydad but you got to win first, it's not going to be easy. Also you got to understand the group, we should not be emotional. We need to be smart and know that, yes we can win, but sometimes if it's difficult don't risk everything and open up.
"Because I think you could also agree with me that we could've beaten Wydad here. The Togolese side and the team from Guinea-Conakry, I think they can also struggle at home.
"If we play our combination passes like we did against Barcelona we should be able to win our two matches at home [against AS Togo-Port on July 27 and Horoya on August 28]," concluded Mosimane.
Downs, who arrived in Conakry on Friday, have been boosted by the return from suspension of PSL Footballer of the Season nominee Percy Tau.