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.
Wales head coach Warren Gatland and captain Sam Warburton say their first prioirty on Sunday in the opening game of the World Cup is to win against Uruguay and not get overly concerned with points difference.
With only days to go until the biggest rugby competition in the world begins, rugby fans visiting Cardiff this autumn will be able to enjoy a special display at National Museum Cardiff as part of the celebrations surrounding the Rugby World Cup.
Geraint John has taken up the new role of WRU elite coach development manager having arrived in Wales last week. WRU TV caught up with him at the WRU rugby department's strategy day at the Millennium Stadium.
The entire Welsh Rugby Union Rugby Department gathered at the Millennium Stadium earlier this week where WRU Head of Rugby Josh Lewsey looked back on a year where structural and strategic changes have seen significant progress made
The Welsh Rugby Union has released a specially produced video to spearhead a new campaign to help promote the values of rugby union. The video, entitled Let us Play underpins the WRU rugby department's philosophy - to engage, transfer and retain players, coaches and referees.