Ospreys have lost just one of their last eight fixtures against fellow Welsh regions: 16-25 to Scarlets at Liberty Stadium on 26 March.
Cardiff Blues five game winning run in the Guinness PRO12 was snapped at home to Leinster on Saturday.
Blues have won their last four away games in the Championship to equal their best ever sequence on the road set in 2010.
Ospreys have won their last ten PRO12 fixtures against Blues since a 21-all draw at Liberty Stadium in April 2011, whilst the capital side's most recent Championship victory over their western neighbours came at the Cardiff City Stadium on New Year's Eve 2010.
Overall Guinness PRO12 head to head record:
Played 26, Ospreys won 18, Blues won 7 with 1 game drawn.
At Liberty Stadium, 7.35pm. Live on BBC Wales
Referee: Nigel Owens (WRU, 138th competition game)
Assistant Referees: Sean Brickell, Gareth Newman (both WRU)
Citing Commissioner: Aurwell Morgan (WRU)
TMO: Tim Hayes (WRU)
Guinness PRO12
Suite 208, Alexandra House,
The Sweepstakes
Ballsbridge, Dublin 4, Ireland