The reigning European champions Chelsea will face Sparta Prague in the last 32 of the Europa League.
The Blues, who failed to make the knockout stages of the top-tier Champions League competition, will start their bid to become only the fourth club after Juventus, Ajax and Bayern Munich to win all of the major European trophies as they bid to usurp the champions Atletico Madrid.
Chelsea avoided a rematch with Atletico, who handed them a 4-1 drubbing in the Super Cup back in August, and as a seeded team will start their Europa League campaign in Prague.
Atletico drew the Russian side Rubin Kazan as they bid to defend the title they won with a comprehensive 3-0 defeat of Athletic Bilbao in last year's all-Spanish final.
Liverpool, the English Premier League side, travel to Zenit for their opening last-32 match against the Russian side who hit the headlines this week when their largest supporters group, Landscrona, caused widespread outrage.
They posted an open letter on their website that outlined their preferred criteria for future signings at Zenit to exclude sexual minorities and non-Europeans from the playing staff.
Tottenham Hotspur will face Lyon, who are a tough opponent more used to Champions League football. Spurs could line up a last-16 meeting with Inter Milan if they can beat Lyon over two legs, and if the Serie A side can win their tie against Romania's Cluj.
It would be a much-anticipated match and evoke memories of when Gareth Bale scored a hat-trick at the San Siro for Tottenham against Inter in a Champions League match that eventually saw the north London side lose 4-3 in October 2010.
Darren Eales, Tottenham's general secretary, expects a hard game against the Ligue 1 side.
"It's a tough draw and this is the first time in nine years they've not been in the Champions League," Eales told Sky Sports News.
"There are a lot of tough teams in the draw. We can ask Hugo [Lloris, Tottenham's former Lyon goalkeeper] the way to go and I think he will be excited about the chance to go back to his old team and play there.
"If we do get Inter if we do get through, two years ago in the Champions League when Gareth Bale got that wonderful hat-trick - that's an exciting game but we have to think about Lyon first."
Eales added Andre Villas-Boas, the Tottenham manager, would continue to treat the competition with respect and would not rest players.
"We want to be playing in European competition. We don't see why we can't have a successful Europa League campaign and do well in the league," he said.
In the other games, Champions League dropouts BATE Borisov face Turkey's Fenerbahce while Spain's Levante take on Olympiacos and Dynamo Kiev take on Ligue 1's Bordeaux in their knockout ties.
The Dutch champions Ajax host Steaua Bucharest first in their last-32 tie while Germany's Stuttgart host the Belgian side Genk and Bayer Leverkusen play Portugal's Benfica.
Borussia Monchengladbach face Lazio while the Swiss champions Basle play Dnipro of Ukraine, Russia's Anzhi play Hannover and Napoli take on the Czech side Viktoria Plzen.
The Newcastle United manager Alan Pardew acknowledged his club's Europa League adventure in Ukraine will be a trip into the dark.
The Magpies, who were paired with Metalist Kharkiv, face a lengthy journey as well as a tough tie when the competition resumes in February.
Asked what he knew about their next opponents, Pardew said: "Not much, really. I do know it's a long journey, I've had a look at that, and they won their group, so it's a tough agenda for us.
"It's a tough draw in terms of travel; the opposition, I know very little about. I can't even comment on that until such time as we do some studying."
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