The winners of the Cilfynydd-Narberth encounter have a trip to premier club Bedwas, but just as important is at Dolgellau, where a win over Aberavon Quins would mean that the home club would join Llangefni in flying the North Wales flag.
Treorchy face an awkward tie against Pencoed at the Oval, while Dunvant are powerful visitors to Abercarn and Bonymaen are a Division One club in action at Trebanos.
Centenary-celebrating Amman Utd are at home against Tonna and Llandybie face high-flying Pontyberem, while Betws have tough opposition from Newport Saracens, as do Pontycymmer at home to Bryncoch.
In-form Banwen are hosts to Tylorstown and Newcastle Emlyn will find hard
opponents in the successful Fairwater club.