Leaders Narberth go on the road face Bonymaen, which means a quick return to Parc Mawr for Otters full back Adrian Killa, who played at scrum half for Bony last season.
Pontypool, in second place after defeating Aberavon on Saturday, will have a difficult match at Pandy Park, Tondu, where the home side are always difficult to beat.
Pontypool, like Naberth, have won all their four matches so far, but will be without skipper Mark Jones, who is out with a broken arm.
Cross Keys, also unbeaten after three wins and a draw, will have a tough task as they meet fellow Gwent club Tredegar, who are another tough club to beat at home.
Bedwas, after impressive wins at Carmarthen and Newbridge, will entertain Llandovery in what should be an entertaining match at Central Park, while Rumney will be hoping to record their first win of the season as they play host to Beddau for the first time in a league meeting.
Whitland meet Llanharan, who have already won twice under their new coach Dennis John, and Carmarthen Quins should overcome an improving Treorchy side.
Aberavon coach Chris O'Callaghan will be keen to see the Wizards back on the winning trail at home to Glamorgan Wanderers and Blackwood meet Newbridge in what is likely to be a keenly-contested local derby.
Divison 1 Fixtures. 24th Septemeber
Aberavon v Glamorgan Wanderers;
Bedwas v Llandovery;
Blackwood v Newbridge;
Bonymaen v Narberth;
Carmarthen Quins v Treorchy;
Rumney v Beddau;
Tondu v Pontypool;
Tredegar v Cross Keys;
Whitland v Llanharan.
Despite drawing with Ireland in the opening round of the RBS 6 Nations, Wales defence coach Shaun Edwards believes the championship 'is still in our hands' as he prepares his side to face Scotland at Principality Stadium tomorrow.
Meet the members of the WRU's inaugural Youth Board - after an online selection process which saw a host of high calibre candidates submit video applications the WRU has made its first 15 appointments.The board is made up of individuals aged between 16 and 21, and will meet for the first time at Principality Stadium on Monday 15th February.
The Wales Women's team headed to Dare Valley Country Park on a team bonding exercise as the entire squad got together for the very first time in preparation for this season's Six Nations championship which kicks off on Saturday with a clash against defending champions Ireland, in Donnybrook.
Wales Head Coach Warren Gatland discusses his team selection for the opening round of the RBS 6 Nations where he leads his side against Ireland, on Sunday. As WRU TV's Luke Brodley discovers, Gatland is fully aware of the challenges the defending champions pose