Manchester United will face Rostov in the last 16 of the Europa League, while Lyon is up against Roma.
Friday's draw in Nyon paired Jose Mourinho's men, who are favourites to win the competition, with the Russian Premier League side.
United is away in the first leg — initially scheduled for March 9 — with the second leg expected to be played at Old Trafford on March 16.
The long journey may present a challenge for Mourinho, with the two legs coming either side of the away FA Cup quarterfinal against Chelsea scheduled for Monday March 13.
Two of the main contenders to win the tournament will do battle in the tie of the round, with Ligue 1 Lyon doing battle with Serie A heavyweights Roma, Bruno Genesio's men at home for the first leg.
The draw — made by former Barcelona and Bayern Munich defender Patrick Andersson — was unseeded with no country protection.
And an all-Bundesliga meeting between Schalke and Borussia Monchengladbach was another exciting tie to be pulled out of the hat, while Belgian teams Gent and Genk will also clash.
LaLiga outfit Celta Vigo plays Krasnodar and Greek champion Olympiacos takes on last season's Turkish Super Lig winner Besiktas.
The other ties see APOEL meet two-time finalist Anderlecht, while 1992 winner Ajax is up against Copenhagen.
Full Europa League last-16 draw:
Celta Vigo v Krasnodar
APOEL v Anderlecht
Schalke v Borussia Monchengladbach
Lyon v Roma
Rostov v Manchester United
Olympiacos v Besiktas
Gent v Genk
Copenhagen v Ajax
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