The Welsh All Blacks are chasing a record third successive Premiership title but cannot afford to drop points after three losses already this season. A win against second from bottom Bedwas is far from assured but an upset would raise serious questions over Neath's championship-winning credentials.
At the Talbot Athletic Ground fifth-placed Aberavon play host to visiting Swansea, who sit fourth from bottom. The Wizards are only six points adrift of Newport at the top of the pile and a win against the struggling All Whites would keep them in the chase for a top-three finish.
Swansea meanwhile have registered just nine points so far this term and crashed 25-0 to local rivals Bridgend in their last outing. An improvement is a must if the St Helens outfit are to move up the table and avoid a relegation dog-fight in the New Year.
At the Arms Park, fourth placed Cardiff face second placed Ebbw Vale, who are three points behind table-topping Newport but hold a game in hand. A win for the Steelmen in the capital would send them joint top and ensure they stay ahead of Rowland Phillips's record-chasing Neath.
Llanelli and Pontypridd go head to head at Stradey Park with the visitors just one point adrift of their hosts in the table. Last season Llanelli clinched an impressive double over Simon King's Ponty as they triumphed 29-19 away at Sardis Road and 18-13 in the return fixture at Stradey Park.
In this evening's other fixtures Cross Keys meet Maesteg at Pandy Park with the visitors boasting a two point advantage in the table. At Church Bank, third from bottom Llandovery clash with Bridgend in what promises to be a tightly fought contest.
At the Memorial Ground on Wednesday Glamorgan Wanderers lost out 11-23 to league leaders Newport who continue their impressive run of form.