United topped Group F ahead of Villarreal before Christmas but were handed a tricky draw in the shape of Atletico who were runners-up to Liverpool in Group B.
Jurgen Klopp's Reds did beat the Spaniards home and away in the group stages to give United confidence but Diego Simeone's side are always a tough opponent.
United have been improving under Ralf Rangnick recently and haven't lost since January 3.
They beat Leeds in a 4-2 thriller in the Premier League on Sunday and will want to get a positive result in Spain to take back to Old Trafford for the return leg.
Atletico have struggled for form recently but claimed a much-needed 3-0 win at Osasuna in LaLiga on Saturday.
Atletico v Man United: talkSPORT coverage
The Champions League round of 16 first-leg tie will kick-off at 8pm on Wednesday, February 23.
Commentary will come from Jim Proudfoot and former England defender Stuart Pearce.
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Atletico v Man United: Team news
United came through a bruising encounter with Leeds over the weekend unscathed but will likely make changes.
Edinson Cavani remains their only confirmed absentee.
Paul Pogba went off early against Leeds but is fine and should start in Spain.
Marcus Rashford, Raphael Varane, Anthony Elanga, Alex Telles and Fred could also come into the line-up after starting from the bench on Sunday.
Atletico v Man United: Who are Atelti?
Having led Atletico to LaLiga glory for the second time last season, Diego Simeone has endured a frustrating campaign to date.
Simeone's men currently lie in fifth place in Spain, 15 points behind arch-rivals Real Madrid at the top of the table.
They have lost seven league games to date this season, three more than in the whole of the last campaign and had their domestic cup hopes shattered by Copa del Rey and Spanish Super Cup exits inside a week last month.
They emerged from Group B as runners-up behind Liverpool despite losing 3-2 at home to the Reds and 2-0 at Anfield, and went out of the competition at this stage last season to eventual winners Chelsea following a 1-0 defeat at the Metropolitano and a 2-0 reverse at Stamford Bridge.
However, they did beat United over two legs the last time the clubs met, in the second round of the European Cup Winners' Cup in 1991-92.
Evergreen striker Luis Suarez will hope to renew his rivalry with the men from Old Trafford, but Antoine Griezmann is yet to figure since his return from a thigh injury.
Atletico v Man United: What has been said?
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