And though the Blues must travel to the Liberty Stadium, Danny Wilson's team have had plenty of time to prepare since playing their Challenge Cup game against Harlequins last Thursday.
The Ospreys have won their last eight PRO12 contests with the Blues but the visitors do pose a try-scoring threat.
Indeed, only Ulster and Connacht have crossed over as many times at the Blues - 23 - this PRO12 season, which has already yielded 186 tries.
One of the other standout fixtures comes at Thomond Park as second-placed Munster welcome table-topping Connacht in an Irish derby with everything riding on it.
Whoever emerges victorious will likely head up the table and with both teams unbeaten in Europe, they come into the game in fine form.
As well as six wins from seven in the league, the men from Galway began their European campaign with back-to-back wins - now they return, in search of a first triumph at Thomond Park since 1986.
They face a Munster side in similar form, Anthony Foley's charges having also lost just once so far this season.
That is not the only derby taking place in Ireland this weekend, with Friday's action also featuring a huge encounter between Leinster and Ulster at the RDS.
Currently battling out for fourth place in the GUINNESS PRO12, both will be keen to make up for disappointing starts to their European campaigns.
Ulster travel to Leinster seeking just a second victory over their provincial rivals in Dublin since 1999 and they will also seek to put an end to their rhythmic sequence of league results this season - WLWLWLW.
Leinster's Mike McCarthy is in line to make his 150th GUINNESS PRO12 appearance, while Isa Nacewa and Craig Gilroy are seeking to add to their tally of four tries apiece in the competition this season.
Elsewhere, GUINNESS PRO12 champions Glasgow Warriors welcome a Benetton Treviso side still chasing a first win of the season.
The Warriors are on a run of 15 PRO12 games without finishing the game empty-handed while Treviso are looking to snap a 16-game winless streak in the league.
And Zebre, fresh from a thumping win over Worcester in Europe, will be looking to take that form into their clash with Scarlets in Llanelli - however Wayne Pivac's side are unbeaten at home in the league this season.
Scarlets flyer DTH van der Merwe could move into fourth spot of the competition's all-time top try-scorers alongside Shane Horgan (39) should he cross over.
Last but not least, Edinburgh host Newport Gwent Dragons at BT Murrayfield. The Dragons are yet to beat non-Italian opposition in the GUINNESS PRO12 this season, though it was against Edinburgh that they ended a five-game losing streak last season, in round 21.
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