Manchester United will come up against their former striker Robin van Persie after being drawn in a tough Europa League group on Friday alongside Fenerbahce, Feyenoord and Zorya Luhansk.
Three-time European champions United must negotiate a competitive group if they are to win one of the few titles that has eluded them.
The Premier League side will face 19-times Turkish champions Fenerbahce, who missed out on the Champions League group stage after a 4-3 aggregate defeat by AS Monaco in the third qualifying round.
They are managed by former Netherlands coach Dick Advocaat and include ex-United forward Van Persie who began his career with Feyenoord.
The Dutch Cup holders finished third in the Eredivisie last season. Zorya qualified as Ukraine’s fourth-placed team.
Southampton, the Premier League’s other representatives, have been drawn alongside Inter Milan, Sparta Prague and Hapoel Be’er Sheva.
Villarreal, beaten semifinalists last season, meet former European champions Steaua Bucharest, FC Zurich and Osmanlispor.
Group-stage first-timers Dundalk of Ireland meet AZ Alkmaar, Maccabi Tel Aviv and Zenit St. Petersburg, who reached the Champions League round of 16 last season.
The top two teams from each of the 12 groups advance to the round of 32 where they will be joined by the eight third-placed teams from the Champions League group stage.
The final will be played in Stockholm on May 24.
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