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It is the final round before the group stages that bring the opportunity for six more matches and a great footballing education as teams from across the continent do battle.
Siyanda Xulu has been included in the FC Rostov squad for their difficult tie against Turkish side Trabzonspor, a team that Xulu has ironically been linked with in the past.
Rostov, who have started the season poorly with Xulu spending all but 26 minutes on the sidelines, are away first and will hope to limit the damage to give themselves something to fight for at home.
It is the first taste of European club football for the Bafana Bafana defender and comes after Rostov won the Russian Cup last season. They had initially been barred from competing in the Europa League on financial grounds, but successfully appealed the decision.
Kamohelo Mokotjo is likely to also get his first run having never played in European club competition while at Feyenoord.
Now at FC Twente, he can look forward to an away tie at Azerbaijan club Karabakh Agdam, a side they would expect to beat.
Nhlakanipho Ntuli has not been included in the Twente squad for this phase of the competition.
Ayanda Patosi has played in Europa before during the 2012-13 season and is set for a high profile return as his Lokeren side tackle English Premiership Hull City.
Patosi has not played yet this season with a knee injury, but returned for a reserve league fixture on Monday and should be fit enough to take a place on the bench.
May Mahlangu (Goteborg), Joel Untersee (Vaduz), Lebogang Phiri (Brondby), Dani Amos (Hapoel Tel Aviv) and Cheyne Fowler (VPS) have already played in, and exited, the Europa League this season, while Steven Pienaar's Everton will join the competition in the group phase.