Wins for former African champions Etoile du Sahel of Tunisia and DR Congo's TP Mazembe will see them progress to the last eight of the Champions League.
Esperance can also progress to the quarter-finals with a win but need other results to go their way as well.
But 2016 winners Mamelodi Sundowns need a win to keep their hopes alive.
All four teams play in the fourth round of matches in the groups sage of the tournament this weekend.
In Group A Esperance of Tunisia travel to Uganda to face KCCA on Saturday knowing victory will all put them on the verge of reaching the last eight.
Esperance's progression will be confirmed if they win and then later on Saturday Egypt's Al Ahly also win in Botswana against Township Rollers.
First-time qualifiers KCCA threw away a two-goal lead last week as they lost 3-2 at Esperance and have already caused an upset with a 2-0 win over visiting Al Ahly in May.
Ahly have recovered from that shock and will close in on a place in the last eight with a second straight win over Rollers, who they beat 3-0 in Egypt last week.
Mazembe lead the way in Group B boasting the only 100% record in the group stage so far.
A fourth straight win on Saturday for the five-time winners in Algeria over Mouloudia Alger will see them reach the quarter-finals.
But it took Mazembe until the 88th minute to score the only goal of the game the Elia Meschak and seal the win over Mouloudia in DR Congo last week.
Former winners Entente Setif of Algeria are third in the group on three points thanks to their win last week over Difaa el Jadida, who have single point.
Those two sides meet on Friday evening in Morocco.
Group C is tight with defending champions Wydad Casablanca of Morocco and Guinea's Horoya both on five points.
The two meet on Saturday in Morocco with Wydad's Tunisian coach Faouzi Benzarti insisting he sees "no reason why Wydad cannot retain the title."
South African champions Mamelodi Sundowns are looking to bounce back from last week's shock loss at Port of Togo as the two meet on Friday evening near Pretoria.
Sundowns, the African champions in 2016, are currently bottom of the group with just two points while Port are a point ahead of them.
Tunisia's Etoile du Sahel will seal one of the quarter-final spots for Group D with a win over the visiting Mbabane Swallows from eSwatini (formerly Swaziland) on Friday.
Etoile, who won the title in 2007, will be full of confidence having beaten Swallows 3-0 in eSwatini last week.
Karim Aouadhi, Maher Hannachi and Amine Chermiti scored the goals as the north Africans exploited their set-piece superiority.
A win for hosts Primeiro Agosto of Angola or Zesco United of Zambia in Luanda, also on Friday, could ultimately decide which of them progresses, almost certainly as runners-up.