However, a last gasp drop goal from Daniel Biggar means the winner of next Tuesday's game between the Ospreys and Scarlets will qualify to play the Blues in the final.
Lee Halfpenny got the scoreboard moving with an early penalty, but James Bird levelled matters on 20 minutes with the Blues' first point of the night.
Bird's kick signalled a wonderful 20 minutes for the Ospreys during which time Biggar and Dean Ronan bagged tries to give the home side a comfortable 13-3 interval lead.
However, it was all change in the second half as the Blues struck back with tries from tries from Rhys Dyer and Lee Collier to lead 15-13.
That was when Biggar stepped up to the mark, dropping a goal from all of 40 metres to earn the Ospreys a crucial win.
The Blues had a last minute penalty awarded to them but opted to take a quick penalty which ended with captain Rhys Dyer being bundled into touch in goal. Final Score NSO 16 CBS 15
Blues Player Development Manager Gafyn Cooper said the Blues players can take credit for their second half comeback. Our attacking game caused problems for the Ospreys out wide but it wasn't to be on this occasion. The Blues will channel all their focus towards the final on April 30th at the Millennium Stadium which kicks-off at 1pm.