Llanharan have a tough task to stay at the top of One East when they travel to Virginia Park to take on a Caerphilly side only three points behind them in the table.
The Dairymen could be overtaken by Merthyr, who visit a Penallta outfit still smarting from their heavy defeat last week, or by Newbridge who entertain Rumney.
Bottom-placed clubs Newport Saracens and Ystrad Rhondda meet with the losers left stranded at the foot of the division.
Four clubs are making the pace in One West with leaders Carmarthen Quins hoping to maintain their three point advantage over Tonmawr by beating visitors Felinfoel. The high-scoring Tonmawr outfit, who have played a game less than Quins, play host to Bonymaen while Narberth travel to Maesteg.
The Otters have already bagged 23 tries in their four matches to date but cannot afford to slip as Whitland are unbeaten, only two points behind, and will relish the visit of Carmarthen Athletic who conceded 12 tries on their last away outing.
Treherbert will be looking for points in their trip to Fleur de Lys in Two East. After three matches they have yet to open their account while Fleur already have a victory in the bag. Leaders Llantrisant are at Abergavenny who have lost three times this season so the Black Army should remain in pole position.
Penclawdd have a tough trip to Builth Wells as the Two West leaders have won all four matches this season, but the Cocklemen have won away from home so will not be overawed at meeting the Bulls. There is a bottom-of-the-table clash at Pencoed where the home side entertain Gorseinon with only try count separating the teams.
Rhymney have a tough task in Three East when leaders Gwernyfed visit War Memorial Park. The Brewers have lost both opening matches conceding over 70 points while Gwernyfed are a point ahead at the top of the table. Nelson are handily placed to take advantage of any slip-up against Rhymney and they are home to a New Tredegar side with one bonus point keeping them off the bottom.
Pontyberem have gained maximum points from their first four matches and are already six points ahead of second-placed Cardigan in Three West. They take that record to Lampeter while Cardigan visit bottom club Llanybydder. Aberystwyth are also unbeaten but have played only three games. They entertain a Tumble side that were soundly beaten last time out.
Four clubs are within two points in Four East and it could be all change after the weekend. Leaders Llandaff take on the Squirrels of Rhiwbina in an all-Cardiff clash at Bishop's Field while Monmouth and Machen will hope to keep their unbeaten records against Crumlin and Tredegar Ironsides respectively.
Top plays bottom in Four West where leaders Brynamman play host to Cwmgors. Four clubs are on ten points and two of them, Trimsaran and Tycroes, play each other while Betws visit Tenby and Hendy are at unbeaten Llandeilo.
Abercarn are two points clear at the top of Five East and they entertain Blaenavon while Oakdale, three wins from three outings, put their unbeaten record on the line against Usk.
Swansea Uplands are without a point in Five West and they travel to Milford to play the Mariners who have won their opening three fixtures. Leaders Cefneithen play host to an Aberaeron side that recorded their first victory last weekend.
Carmarthen Quins are holding an exhibition to commemorate club players who fought in World War I. All welcome to the clubhouse on Friday afternoon to learn more about local history, or share any family anecdotes or artifacts.
Defence coach Shaun Edwards believes Saturday's clash against England - the 'form team in world rugby' - poses a huge challenge for his side but he is confident, with Wales beginning to show the defensive qualities displayed in the last two World Cups,