And it doesn't get any easier for the Dragons who face a tricky trip to Dublin to play Leinster this evening.
The Ospreys will be looking to build on their impressive start when they host Edinburgh on Saturday and the history books are on their side with the visitors not recording a win at the Liberty Stadium in the past two seasons.
The Scarlets travel to Galway to play Connacht and will be looking to overturn their defeat at the Sportsground last season.
And in the final game of the weekend, the Blues welcome Benetton Treviso to South Wales.
LEINSTER V NEWPORT GWENT DRAGONS (FRI SEPT 9, KO 19:35)
The Dragons return to Ireland following last weekend's defeat to Champions Munster and continue their search for a first victory across the Irish sea in three years.
They have made two changes to the starting line-up with Ashley Smith (hamstring) and Tom Brown (dead leg) missing out.
NewportGwent Dragons Team:15. Martyn Thomas, 14. Adam Hughes, 13. Tom Riley, 12. Pat Leach, 11. Mike Poole, 10. Jason Tovey, 9. Joe Bedford, 1. Phil Price, 2. Tom Willis, 3. Ben Castle, 4. Adam Jones, 5. Rob Sidoli, 6. Andrew Coombs, 7. Gavin Thomas, 8. Hugo Ellis
Replacements 16. Rhys Buckley, 17. Nathan Williams, 18. Dan Way, 19. Lewis Evans, 20. Jevon Groves, 21. Wayne Evans, 22. Steffan Jones, 23. Jamie Smith
OSPREYS V EDINBURGH (SAT SEPT 10, KO 18:30)
The Ospreys continue with the same team which comfortably beat European Champions Leinster last weekend for the clash against Edinburgh at the Liberty Stadium.
Ospreys Team:15 Richard Fussell, 14 Kristian Phillips, 13 Andrew Bishop, 12 Ashley Beck, 11 Hanno Dirksen, 10 Dan Biggar, 9 Rhys Webb, 1 Duncan Jones, 2 Mefin Davies, 3 Cai Griffiths, 4 Ian Gough, 5 Ian Evans, 6 Tom Smith, 7 Justin Tipuric (Capt), 8 Jonathan Thomas
Replacements:16 Scott Baldwin, 17 Aaron Jarvis, 18 Joe Rees, 19 James Goode, 20 James King, 21 Tom Isaacs, 22 Matthew Morgan, 23 Sonny Parker
CONNACHT V SCARLETS (SAT SEPT 10, KO 15.15)
The Scarlets hand debut's to two new players in the clash against Connacht tomorrow.
20-year-old Swansea wing Liam Williams gets his first opportunity for the region while Ruki Tipuna will make his eagerly awaited debut at scrum-half after finalising his paperwork from New Zealand.
Scarlets team:15 Daniel Evans, 14 Lee Williams, 13 Rhodri Gomer Davies 12 Gareth Maule, 11 Liam Williams, 10 Dan Newton, 9 Ruki Tipuna, 1 Iestyn Thomas (capt), 2 Emyr Phillips, 3 Rhys Thomas, 4 Aaron Shingler, 5 Dominic Day, 6 Rob McCusker, 7 Josh Turnbull, 8 Ben Morgan.
Replacements: Kirby Myhill, Phil John, Simon Gardiner, Lou Reed, Johnathan Edwards, Rhodri Williams, Aled Thomas, Adam Warren.
CARDIFF BLUES V BENETTON TREVISO (SUN SEPT 11, KO 15:45)
Blues duo Lewis Jones and Alex Cutherbert make their competitive debut's for the region on Sunday against Treviso.
In the forwards Michael Paterson moves into the second-row with Maama Molitika coming onto the blindside and on the bench Xavier Rush returns having recovered from his hernia operation.
Cardiff Blues Team:15. Chris Czekaj 14. Alex Cuthbert 13. Gavin Evans 12. Dafydd Hewitt 11. Tom James 10. Gareth Davies 9. Lewis Jones 8. Andries Pertorius 7. Martyn Williams 6. Maama Molitika 5. Deiniol Jones 4. Michael Paterson 3. Scott Andrews 2. T Rhys Thomas (c) 1. Sam Hobbs
Replacements: 16. Rhys Williams 17. Nathan Trevett 18. Ryan Harford 19. Paul Tito 20. Xavier Rush 21. Richie Rees 22. Ceri Sweeney 23. Richard Mustoe.