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.
As the countdown continues for RWC2015, Tournament Chief Executive Debbie Jevans visited the Millennium Stadium to discuss preparations for the eight matches and reveal the positive news that 100,000 tickets for games at the home of Welsh rugby have sold in the last seven days.
Jason Harries is targeting a first win on the World Series circuit this season with Wales. The series returns to action this weekend in Dubai where Harries is part of a team hoping to build from its efforts in round one in October.
Wales skipper Jevon Groves says his side have addressed a few points from Gold Coast and aim to 'hit the ground running' in the next two rounds of the World Series, kicking off with this weekend in Dubai before heading off to South Africa next week.
Wales Sevens manager Steff Thomas is hopeful his side can build from a quarter-final spot in the opening round of the World Series in Australia when his side take part in the forthcoming double header in Dubai and South Africa.