Rowland Phillips's Neath welcome second-placed Ebbw Vale to the Gnoll for a clash which pits top flight champions against pretenders. The Welsh All Blacks have struggled to capture the form that led them to a second consecutive title last year and are currently six points off the pace in the league.
Meanwhile, the Steelmen have been a surprise package this season and will see Saturday's clash as the chance to test their credentials against the title-holders.
Second-from-bottom Glamorgan Wanderers face a tough test when Llanelli arrive at the Memorial Ground on Saturday. The Wanderers moved off the foot of the table with a crucial win over struggling Llandovery last weekend.
Yet just when another win would further aid their plight they must front up to one of the league's form sides. Fourth-placed Llanelli defeated Ebbw Vale last time out and the Wanderers will be under no illusions as to the size of this weekend's task.
At Sardis Road Pontypridd front up to visiting Aberavon on the back of a narrow 7-9 victory over Bridgend last time out. The Wizards also won last weekend, seeing off Bedwas 21-12, and this clash sees two of the league's top sides go head to head.
Aberavon are three points behind leaders Newport with a game in hand, while Pontypridd are seven points off the pace in seventh. Simon King's young side have played some impressive rugby this season and will test the Wizard's title ambitions to the full.
At the Brewery Field Bridgend play host to local rivals Cardiff with the Black and Blues boasting a four point advantage in the table. The Ravens are ninth, four points behind Cardiff, and this contest promises to be hard-fought and could go either way.
Bottom-placed Llandovery welcome mid-table Cross Keys to Church Bank while at St Helens Swansea play host to Bedwas.