Abercarn with only win this season face the hardest task in any division as they go to Eastern leaders Bargoed, hoping to inflict a first defeat for two years on the home side.
Abergavenny will give their unbeaten record its severest task yet as they meet an in-form Senghenydd at Bailey Park, while an all-Cardiff affair pairs Old Illtydians against Llanishen on Rumney Park - a match where Llanishen coach Shaun Lee will be able to walk to.
The Gorseinon-Loughor battle in the West will carry on if both clubs gain home wins over Hendy and Llandeilo respectively, but the most-awaited South-East clash is at the Resevoir Field, where Barry face a strengthened Penygraig team. Tylorstown's trip to North wales to meet Ruthin will also bring a close contest.
Bryncoch will be hoping to keep their unbeaten record intact in the outh-West, but face a difficlu match away to Maesteg Quins in a division that they lead by six points.
Two of three unbeaten Division Four clubs are in the South-East, but they avoid each other as Aberdare are at home to Pontyclun and Fairwater visit Bedlinog.
The West leaders - Amman Utd and Neyland - meet in a huge clash on Cwmamman Park and also in that region there will be a good contest at Cefneithin where Fishguard are the visitors.
East leaders Monmouth go the excellent Diamond Ground to take on Cardiff HSOB and runaway South-West leaders Resolven entertain Trebanos, while Llangefni take on Newtown at Cae Smyma in the North.
Pembroke face their hardest match thus far in the West, as after seven successive wins they travel to New Dock Stars, who have six wins in eight outings.
Top match in the South-East should be at Cilfynydd, where South Wales Police are travelling, while Der's Broncos face an in-form Porth and in the South-West Glyncorrwg sit back to watch rivals irchgrove, Abercrave and Crynant in action.
While Machen and St Alban's are at home in the East, unbeaten Nantyglo face a trip to Bettws and in the North, both Bala and Bethesda are playing away.