Mekelakeya and Wolaitta Dicha will kick off the Ethiopia Premier League Week 19 fixtures at Dire Dawa International Stadium on Thursday.
Mekelakeya are currently third on the table with 36 points, but they will go top of the log if they are victorious.
Mekelakeya are back in action after a crucial 2-0 win over Ethiopia Nigd Bank.
The team will be without their head coach Gebrekisrsto Birara, who is is still serving a ban.
Wolaitta Dicha are 11th with 24 points. They are winless in their last six league matches.
Yared Gemechu's team is without their top scorer, Binyam Fikru, who was also banned for four league matches.
Mekelakeya won their first-first clash 1-0.
In the day's other encounter Ethiopia Coffee face Fasil Kenema in a highly anticipated match.
The two teams are only separated by one point.
Ethiopia Coffee lie in fifth place with 29 points and come into this encounter on a two-match losing streak.
They had gone nine matches undefeated before suffering two defeats in their last two matches.
Fasil Kenema are in fourth place with 30 points.
Wubetu Abate's team are on a three-match unbeaten run, winning twice and earning one draw.
Their first-round clash ended with a 2-20 win for Fasil Kenema.