Balzan Youths will be hoping to stay ahead of neighbours Birkirkara as the two seek precious points in their bid to secure a top six finish.
The Youths won three of the last four matches to climb from seventh to joint-fourth as they defeated Hibernians, Sliema and Marsaxlokk.
On the other hand, after losing 0-1 to Floriana, the Stripes will be hoping to return to winning ways. They lost three out of the last five league matches. A win is a must in order to steer clear of seventh-placed Qormi.
Jean Pierre Mifsud Triganza is set to start for Birkirkara after returning with the club from Sliema Wanderers in a deal which took Trevor Cilia and Andrew Decesare in the opposite direction. Joseph Zerafa returns after serving a suspension but Rowen Muscat is in doubt. Balzan will be boosted with the return of Bledjon Guga, Bjorn Bondin and Jonathan Francica who missed the last game through suspension. However Jamie Pace is ruled out injured.
Birkirkara defeated Balzan 2-1 in the first round.
In the first game, Hamrun Spartans and Mqabba seek maximum points from a direct clash between two teams who are fighting to climb out of the danger zone.
Two teams separate the two teams as Mqabba are currently eighth on 17 points and Hamrun tenth on 15.
The Spartans lost five of the last seven matches, claiming their last league win, two months ago against Tarxien Rainbows and suffering heavy defeats to Qormi and Hibernians last month.
Mqabba, on the other hand, earned two points from the last three matches but like Hamrun have gone two months without a win.
Hamrun welcome back Gianluca Calabretta after serving a one-match ban. David Fenech is expected to make his debut after joining the club from Balzan while Thiago Mazzitelli is set to be included in the starting line-up after recovering from an injury.
In the first round, Hamrun defeated Mqabba 3-2.