If regional bragging rights and the huge crowds weren't enough of an incentive, there is also everything to play for when it comes to spots in the top four and next season's Champions Cup.
The Blues know that a win over their rivals to the West will keep them very much in the hunt for a top-six spot and the chance to qualify for next season's Champions Cup.
Both teams will have plenty of cause for optimism, the Blues have won four in a row in the league, and are looking for a fifth straight success for the first time since 2010.
However the Ospreys have won the last nine matches between the two since a draw all the way back in 2011.
The Blues also have the league's top points scorer in Rhys Patchell, who is currently leading the way with 174 points, 22 clear of Ospreys rival Sam Davies.
At the same venue the Scarlets will be dreaming of a top four spot, and need to beat the Dragons to give themselves the best possible chance.
Recent history is in their favour, with just one loss in the last 15 meetings between the sides, while the Dragons have now lost eight in a row in the league, their worst-ever run.
The Scarlets will also have a keen eye on what is going on in Belfast, where Ulster host Leinster in a massive Irish derby.
A win could get Ulster back into the hunt for a home semi-final, but first and foremost they will be keen to secure a top-four spot.
And that will require a win over Leinster, a team who they have beaten just once in their last seven attempts.
That win came last year at the Kingspan Stadium, in Round 20, but Ulster come into the game on good form, having not lost at home since January.
For Leinster, Luke Fitzgerald could make his 100th league appearance if he is selected, while Paddy Jackson needs 22 points to make it to 500 for Ulster in the Guinness PRO12.
The battle for the top six will go a long way to being decided this weekend when Munster take on Edinburgh at Irish Independent Park in Cork.
The loser of this game will be all but out of the race for a top-half finish, and more importantly, a place in next season's Champions Cup.
And while they have struggled recently, Munster will hope their recent run against Edinburgh continues, having lost just one of their last eight games against the Scots.
You also have to go back a long way for Edinburgh's only win in Cork, a solitary success back in 2004.
While Edinburgh will need to buck a recent trend to stay in the top-six race, one team in no such need of a turnaround in fortunes are the defending champions who are gunning for a record-equalling ninth straight win at home to Zebre on Friday.
Glasgow Warriors have never lost to Zebre, and a win would be enough to secure a play-off spot as they look to retain their title.
Zebre are also looking to hold onto the top Italian spot in the league, synonymous with a Champions Cup spot and might need Connacht to beat Treviso on Friday.
The Irish province are just a point away from reaching the play-offs for the first time since their reintroduction but have not scored a try in Treviso since 2013.
For Connacht Matt Healy will also be looking to extend his lead at the top of the try-scoring charts, with nine to his name to date, one clear of Ulster's Craig Gilroy and Edinburgh's Damien Hoyland.
Treviso, meanwhile, have lost five Guinness PRO12 games on the spin since a win over the Dragons in February.
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