Hibernians will be aiming for the three points from the clash with Floriana in one the four matches in programme at the National Stadium and the Hibernians Stadium.
A win would put the Paolites on top, one point ahead of Hamrun although the Spartans would have a game in hand. Hibs registered three wins in their last three outings, winning five out of the last six matches.
Floriana, on the other hand, are currently eleventh on 18 points after losing four out of the last six matches, earning just two points in draws.
In the first round, Hibernians beat Floriana 3-1.
After suffering back-to-back defeats to Mosta and Hibernians, Sliema Wanderers will be hoping to return to winning ways as they take on Sirens in another match at the National Stadium.
Sliema lost three out of the last five matches and are now fourth, six points behind leaders Hamrun. Sirens, however, are desperate for points after losing three out of the last four matches, only beating Senglea.
Sliema and Sirens shared the spoils in a goalless draw in the first round.
At the Hibernians Stadium, Gudja United also hope to return to winning ways as they take on Lija Athletic after suffering back-to-back defeats to Sirens and Santa Lucia. A win which would put them once again on level points with Valletta in the eighth place.
Lija are coming from a winless streak of twelve matches, earning just three points in three draws.
Gudja defeated Santa Lucia 2-0 in the first round.
In another match, Zejtun Corinthians start as favourites to claim the three points as they face bottom-placed Senglea Athletic.
The Corinthians are unbeaten in three matches following a win over Tarxien and draws with Floriana and Santa Lucia. Senglea, on the other hand, lost the last six matches and are still chasing their first win in this Premier League campaign.
In the first round, Senglea held Zejtun in a 1-1 draw.
All matches are being played behind closed doors. but fans are able to watch games thanks to the live-streaming service being offered by the Malta Football Association at https://live.mfa.com.mt/ apart from the usual two weekly matches which are broadcast on TVM 2 and/or TSN.