They will wrap up their 2018/19 campaign against the Toyota Cheetahs in Bloemfontein on 27 April in the final pool round.
The hosts played with passion in the opening exchanges, but this was not enough to keep Ospreys - who needed to win the match with a bonus-point to stay in the race for a possible playoff spot - at bay.
The visitors broke through with back-to-back tries by Dan Evans late in the first quarter and never looked back courtesy of their fantastic support play and fine vision. This allowed Evans to earn a hat-trick and Bradley Davies a brace.
Such was the high quality of the visitors’ attack, they secured their bonus-point try by the 25th minute, with Cory Allen, Hanno Dirksen and Davies crossing the chalk after Evans to rack up five first-half tries for an encouraging 33-0 halftime lead.
In stark contrast to the Welshmen, the Isuzu Southern Kings struggled to convert a number of try-scoring chances into points due to errors at vital times. Their 14 missed tackles before the break also didn’t assist their cause.
The hosts tightened up their defence in the second half, but they were dealt a big blow 12 minutes into the second half as Stephan Greeff received a yellow card, and Osprey’s took advantage of this as Evans cut through the defence for his hat-trick.
The Isuzu Southern Kings responded well, with Michael Willemse dotting down from a rolling maul, and Masixole Banda adding the conversion.
They had opportunities to add to this, but they paid a heavy price for their mistakes, as a forward pass denied Stefan Ungerer a five-pointer, while Banda was tackled inches short of the chalk with minutes left on the clock.
Ospreys made sure they finished their tour to South Africa strongly with Davies finishing off another enterprising spell on the stroke of fulltime to take their try tally seven for the rewarding 43-7 victory.
Isuzu Southern Kings 7 (0) – Try: Michael Willemse. Conversion: Masixole Banda.
Ospreys 43 (33) - Tries: Dan Evans (3), Cory Allen, Hanno Dirksen, Bradley Davies (2). Conversions: Luke Price (4).