Group B leaders USM won the first clash between the two clubs 2-1 at Setif two months ago, a result that immediately put the defending champions on the back foot.
Setif heads into their penultimate mini-league fixture having secured only one victory and four points from four outings. Even a victory at already-qualified USM would not guarantee Setif a top-two finish and a passage to the semi-finals.
While it is difficult to imagine two-time African champions Setif reaching the semi-finals, assistant coach Riadh Belkhir remains hopeful.
“We have not been eliminated from the competition yet. Merreikh can suffer defeats in their remaining two games," he said of the Omdurman outfit, whose final fixture is at home to USM Alger next month.
“We have to win our next two matches to have a chance of qualifying. That is going to be difficult because every opponent wants to beat the reigning champions and they raise their game,” admitted Belkhir.
“Our players have displayed great determination throughout the group stage and that will not change during the next two rounds.”
Setif have suffered from a lack of goals this season, managing only 10 in eight preliminary and group matches. Leading scorers El-Hedi Belameiri, who was born in France, and Mohamed Benyettou have bagged a paltry two apiece.
A glimmer of hope for Setif is that they deliver better group results when playing away with three victories, three draws and only two defeats from three appearances.
Italian Diego Garzitto, who coached Democratic Republic of Congo club TP Mazembe to the 2009 Champions League title, wants Merreikh to win the group.
“I am confident we will finish at least second, but our aim is to top the final standings,” he told reporters in Sudan.
However, barring an unlikely collapse by 2003 Champions League semi-finalists USM, Merreikh appear on course for a semi-finals showdown with four-time African champions Mazembe.
Group A leaders Mazembe tackle Al Hilal, the great domestic rivals of Merreikh, in Omdurman Sunday and a win will assure them of a last-four place.
Although Hilal are reeling from a shock home loss to Moroccans Moghreb Tetouan two weekends ago, Mazembe will be wary having lost away to the Sudanese side at the same stage last season.
“We still have a chance of qualifying,” insists Tunisia-born Hilal coach Nabil Al Kouki, whose side share second place with Tetouan, three points adrift of Mazembe.
“Our game against Mazembe will be crucial -- nothing but three points will suffice," said Al Kouki.
Tetouan, who drew two previous home group games, host Smouha of Egypt, who have lost all five preliminary and mini-league away matches, in another Sunday fixture.
23.08.2015 20H00 El Hilal (Sudan) vs TP Mazembe (DR Congo)
23.08.2015 20H30 Moghreb Tetouan (Morocco) vs Smouha (Egypt)
21.08.2015 20H30 USM Alger (Algeria) vs ES Setif (Algeria)
22.08.2015 20H30 MC Eulma (Algeria) vs El Merreikh (Sudan)
*All times are in local time