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.
WRU TV were on hand at the launch of a major new commercial deal with WRU and Mercedes-Benz South Wales (part of the Sinclair Group), which sees the family company become an official supplier to the Welsh Rugby Union
On the back of the recent Women's Rugby World Cup, the WRU has launched a revitalised Women's and Girls domestic seasonal structure, and the future is looking bright.
Go to www.wru.co.uk/tryourgame for more information
Roger Lewis talks to WRU TV at the announcement of a new £60 million Rugby Services Agreement (RSA) which provides a new and positive contractual relationship between the WRU and its four Regions for the next six years has been agreed.
The Welsh Rugby Union has announced a major new sponsorship deal with Gullivers Sports Travel which will make the UK's leading, and longest established, multi-sport tour operator, an Official Supplier for the rest of the decade.
Having taken part in seven World Cups as a player and coach, Liza Burgess hopes to go out in style this afternoon when Wales take on Australia in the Play-off for seventh and eighth place in the Women's Rugby World Cup in Paris.