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Fly-half Steffan Jones kicked six penalties for Newport Gwent Dragons as the Ospreys were despatched 18-14 at a drenched Rodney Parade.
It was the Dragons' first win in the competition this season although the match only came to life in the final quarter, after Ospreys flanker Jonathan Thomas scored the only try of the evening.
Matthew Morgan kicked three penalties for the visitors but they were not helped by having to play 20 minutes of the match with 14 men through two sin-bins, against one for the Dragons.
The defeat leaves the Ospreys third in Pool Four with five points from their three matches, while Dragons remain bottom of Pool One with four points.
Jones landed three penalties against one from Morgan in the early exchanges, but that was scant reward for the West Walians as they played against 14 men when home No 8 Ieuan Jones was sin-binned for deliberately not rolling away from a ruck under his own posts.
However, that man advantage for the Ospreys was wiped out when Morgan Allen also saw yellow as the referee penalised the visitors for persistent infringements.
There were a couple of try chances during the half but, as the rain swept in, the game turned into a muddy stand-off between two determined packs and stubborn defences.
When the Dragons gave away kickable penalties within range of their posts, Morgan made them pay with two efforts to level the game at 9-9 at the break.
Ospreys then put themselves in the driving seat from a lineout just metres from the Dragons line, rucking the ball powerfully before former Wales back row Thomas twisted his way over for the try.
And, from there, the game suddenly sprang into life as Jones booted his fifth penalty, but the Ospreys again found themselves down to 14 men in a critical part of the match when skipper and scrum-half Rhys Webb high-tackled home No 8 Jones and was yellow-carded with 11 minutes left.
Jones made the Ospreys pay for more indiscipline with his sixth and final penalty and, despite some later pressure, the home line held firm to deny the 2008 Cup champions.