The Dragons host the Scarlets at Rodney Parade (KO 7.30pm) with both teams having ambitions of winning the inaugural competition. In the other game the Ospreys travel to Glamorgan Wanderers to take on the Blues (KO 7.15pm).
In the Rodney Parade battle, there will be an interesting clash in the back row where the Scarlets young pretender Sioned Harries will take on experienced Welsh international Jamie Kift.
Kift, the Dragons captain, was in outstanding form for the Dragons in their narrow 6-0 victory over the Ospreys in the last round while Harries impressed in the Scarlets back row against the Blues.
Their battle at the breakdown will be keenly observed by Wales senior coach Jason Lewis who names his World Cup squad early next week.
Kift, however, is playing down the battle. "I'm just concentrating on my own game. From a team perspective this is another challenge for us, as is every game. The games have been really close, the first one we won with the last move of the match and the last one we only won 6-0. Defensively we have been superb.
Several other up and coming players have a last chance to impress before Lewis dots his Is and crosses his Ts on his final squad.
"This is definitely a level up from club rugby and the girls have responded to it," said Kift. "Just look at Megan [Williams]. She came on for Wales Under 20s on Sunday and was in a side which beat England. She was identified in these games - she wouldn't have been given the chance if it wasn't for this competiton. There are definitely one or two girls who have put their hands up for selection.
Both teams have beaten the Ospreys and Blues in what were very close encounters and both are out for a clean sweep.
The regional rugby showdown between Dragons and the Scarlets will be the first time a women's regional game has been hosted on the home ground of their male counterparts, a fact WRU Women's Community Rugby Manager Nicola Smith is particularly proud of.
"We are extremely pleased that the Dragons are supporting women's rugby and hope that other regions will follow suit in the coming seasons," she said.
Ospreys: 15 Kerin Lake 14 Charlie Murray 13 Adi Taviner12 Swian Lillicrap11 Nicola Davies10 Bethan Preece 9 Sian Moore; 1 Alex Stokes 2 Amy Lawrence 3 Bethan Howell
4 Sian Williams 5 Shouna Powell-Hughes 6 Carys John 8 Rachel Taylor7 Lisa Newton
Substitutes: Laura O'shea Carol-Ann Burt Carys Phillips Kathryn Joseph Rhianydd Morgan Jamie Davies.
Blues: 15 Larissa Muldoon 14 Rachel Green 13 Levi Hallett 12 Zoe Wells 11 Kiri Bennett 10 Ceri Bowen 9 Laura Prosser: 1 Kate Hutchings 2 Becky Newton 3 Lowri Harries 4 Gemma Hallett 5 Nia Sian Jones 6 Rachel Cork 8 Catrina Nichols 7 Megan Snape
Substitutes: 16 Nat Stone, 17 Sam Baker, 18 Amy Kelland 19 Vikki Gaylard 20 Emma Winch 21 Anna Jenkins 22 Sally Tuson.
Dragons: 15 Megan Williams 14 Ceri Bailey 13 Kim Boaler 12 Leila Johns 11 Victoria White 10 Aimee Young 9 Yasmin Leung; 1 Caryl Thomas 2 Rhian Bowden 3 Hannah Roberts 4 Mara Roberts 5 Tanyer Price 6 Sian Williams 8 Beth Hawke 7 Jamie Kift (c)
Substitutes 16 Claire Lilley 17 Megan Yorke 18 Hari McCormick 19 Jess Wilson 20 Anna Mills 21 Paige Portman 22 Lianne Vokes 23 Kerry Jenkins
Scarlets: 15 Non Evans 14 Caryl James 13 Naomi Thomas 12 Elen Evans 11 Heledd Stephens 10 Awen Davies 9 Jess Kavanagh; 1 Catrin Edwards 2 Sara Davies 3 Sophie Mangano 4 Chloe Howells 5 Kath Gravell 6 Sioned Harries 8 Vicky Owens 7 Nia Davies
Substitutes: 16 Sian Morgan 17 Ceris Davies 18 Cath Davies 19 Rebecca Norris 20 Emma Summons 21 Jodi Evans 22 Lowri Evans 23 Tammy Howells