The Saints finished seventh in the Barclays Premier League last season and so were among the sides for Friday's draw in Nyon, Switzerland
The fixture will see Southampton manager Ronald Koeman return to Holland, where he was coach at Feyenoord before moving to England
West Ham, meanwhile, will defend a slender 1-0 lead over Birkirkara in the second leg of their second qualifying round when they head to Malta following a 90th-minute goal by James Tomkins at Upton Park
Inverness will have to overturn a 1-0 deficit against FC Astra of Romania after losing at home in the first leg
Aberdeen are 3-0 up in their second-round tie with HNK Rijeka of Croatia and so look on course to meet either Kairat Almaty of Kazakstan or Armenian side Alashkert in the third round
There are other British and Irish sides still involved in the Europa League qualifiers.
Shamrock Rovers are 2-0 down against Odd of Norway, and would tackle either Randers of Denmark or Sweden's Elfsborg if they make it through to round three.
University College Dublin trail Slovan Bratislava 1-0
The winners of that tie will meet Russian club Krasnodar.
Northern Irish side Linfield are 2-1 down to Spartak Trnava of Slovakia
Should they go through, Linfield would play Croatians Lokomotiv Zagreb or Greek side PAOK
Welsh club Newton lost 2-0 at FC Copenhagen, with the winners of that tie drawn against Czech team Jablonec.
The Europa League play-off round will start at the end of July, and will include the 15 losers out of the Champions League third qualifying round.
Premier League clubs Tottenham and Liverpool are both automatically qualified for the group stages.
Source : PA