Manchester United will face French side Saint-Etienne in the Europa League last 32, while Tottenham Hotspur meet Belgian team Gent.
United midfielder Paul Pogba is set to face older brother Florentin, who plays for the eighth-placed Ligue 1 side.
Spurs have never met Gent, who finished third in the Belgian top-flight last season, in a competitive fixture.
United’s first leg will be played on Wednesday, 15 February, while Spurs play the following day.
The Red Devils will play on Wednesday because Saint-Etienne’s neighbours Lyon are also playing at home in the Europe League that week.
Both return legs will be played on Thursday, 23 February.
The two Premier League clubs could not be drawn together as teams from the same nation are kept apart.
Tottenham, along with the other seeded teams, will be at home in the second leg.
Spurs were seeded after dropping down from the Champions League, while United were unseeded after finishing second in Group A.
But Jose Mourinho’s side are still favourites to win the competition with most bookmakers.
The Europa League final will be held at Stockholm’s Friends Arena on 24 May.
Pogba versus Pogba
Manchester United’s tie with Saint-Etienne will see Paul Pogba face his older brother Florentin, 26.
“It’s nice, it’s a nice thing,” said Mourinho. “Paul will be laughing, and for sure his brother will also be laughing.
“I think it’s nice, it’s happened in the history of football a few times and it’s nice.”
After a group stage that involved a 3,000 mile round trip to Odessa in Ukraine, Mourinho also welcomed a tie that is much closer to home.
“The good thing is the travel,” he added. “We were very unlucky in the group stage, now we go to France.”
Athletic Bilbao (Spain) v Apoel Nicosia (Cyprus)
Legia Warsaw (Poland) v Ajax (Netherlands)
Anderlecht (Belgium) v Zenit St Petersburg (Russia)
Astra Giurgiu (Romania) v Genk (Belgium)
Manchester United (England) v Saint-Etienne (France)
Villarreal (Spain) v Roma (Italy)
Ludogorets (Bulgaria) v FC Copenhagen (Denmark)
Celta Vigo (Spain) v Shakhtar Donetsk (Ukraine)
Olympiakos (Greece) v Osmanlispor (Turkey)
Gent (Belgium) v Tottenham Hotspur (England)
Rostov (Russia) v Sparta Prague (Czech Republic)
Krasnodar (Russia) v Fenerbahce (Turkey)
Borussia Monchengladbach (Germany) v Fiorentina (Italy)
AZ Alkmaar (Netherlands) v Lyon (France)
Hapoel Beer Sheva (Israel) v Besiktas (Turkey)
PAOK (Greece) v Schalke (Germany)
Man Utd have hosted Saint-Etienne before – in Plymouth…
Don’t worry, you have read that headline correctly.
Manchester United have only met Saint-Etienne twice before – in a two-legged European Cup Winners’ Cup tie in 1977-78.
And the Red Devils were ordered to play the second leg in Plymouth after the first leg in France was marred by violence involving United supporters.
The English side were kicked out of the competition by Uefa but were reinstated on appeal and told to play their home game outside Manchester.
Bizarrely they chose the Devon city, winning 2-0 to go through 3-1 on aggregate.
United fancy playing the French
- Manchester United have lost just one of their last 16 matches against French opposition, winning nine and drawing six
- United’s former Paris St-Germain striker Zlatan Ibrahimovic has scored 14 goals in 13 games against St Etienne – his favourite opponent in all competitions
- Tottenham have played Belgian opponents eight times in Europe – remaining unbeaten at home (W3 D1) but winless away (D2 L2)
- A new Europa League winner will be crowned for the first time since 2013 after Sevilla, triumphant in each of the past three seasons, progressed to the Champions League last 16
- French side Lyon are unbeaten in their last six European meetings with Dutch teams, winning two and drawing four
- German team Schalke have won five out of six European games against Greek sides, drawing the other
- In their previous seven meetings with Italian sides, German team Borussia Monchengladbach have drawn five (winning one and losing one)