The match of the season thus far is expected at the Gnoll when unbeaten leaders Neath take on last season's champions, Newport. Having had three points docked and losing at Ebbw Vale last week, Newport will see this as make or break to topple the Welsh All Blacks.
Just as interesting as the top match will be the Aberavon-Llanelli clash as the four-match run of the Wizards will be on the line against the ten-match winning streak of the second -placed Scarlets. Bedwas, without a home win, take on free-scoring Swansea and Ebbw Vale look for another home win as they face the speedy Cardiff back division.
While Cross Keys and Llandovery meet in a mid-table battle, there is a basement struggle at Llanharan where bottom club Caerphilly are the visitors in an important match. Other strongly-contested games will be between Bridgend against Pontypool and Pontypridd at home to Newbridge.
The last five years have been an emotional rollercoaster on and off the pitch for RGC1404. Promotion to the Principality Premiership was the culmination of five years of hard work and investment in North Wales. WRU TV caught up with prop Joe Simpson, who was one of the first intake of WRU North Wales Academy players in 2010.
Ebbw Vale captain Damien Hudd picked up the biggest accolade of the night at the 11th Principality Premiership Awards Evening held at Principality Stadium, after leading his side to the title for the first time.
Wales assistant coach Robin McBryde is predicting a tough battle against England on Sunday despite the fact they may not be considered to be at full strength. Players will be out to impress Eddie Jones which makes England a dangerous proposition, he says.
Wales U20 captain Tom Phillips and performance psychologist Dr Rich Neil explain why spending three days at Monmouth RFC has further strengthened the togetherness of the squad ahead of the #WorldRugbyU20s