Reigning champions Neath travel to Pandy Park to take on Cross Keys with hopes of a third successive title hanging by a thread. The Welsh All Blacks are six points adrift of Ebbw Vale and must rely on other teams taking points from the leaders if they are to make history with a third championship in as many years.
The Keys would love to be a thorn in the side of Rowland Phillips's outfit on Saturday and know an unexpected win could lift them into seventh place.
Third from bottom Bedwas will be hoping to avoid defeat when Llanelli come to town as they hover dangerously close to the relegation zone. The Scarlets, meanwhile, will have their sights set on three points which could propel them into contention for a top three finish.
Relegation candidates Llandovery welcome fellow strugglers Maesteg to Church Bank in a good old fashioned six-pointer. The Drovers are three points adrift of Maesteg but a win would offer renewed hope of a last gasp push for survival. The pressure falls on the Old Parish to avoid a loss which would threaten their Premiership status.
On the coast Swansea take on local rivals Bridgend who make the short trip west along the M4. The Ravens currently languish in mid-table while the All Whites sit fourth from bottom, dangerously close to the ongoing relegation dog-fight. A win for Swansea would send them clear of any immediate relegation danger but Bridgend will come out fighting in this local derby.
Elsewhere, at the Talbot Athletic Ground Aberavon play host to Glamorgan Wanderers and at the Arms Park Cardiff front up to fourth placed Newport.