Arsenal faces a challenging matchup against Porto, while defending champions Manchester City will confront FC Copenhagen.
As a result, Arsenal and Man City were seeded in Monday’s draw, automatically avoiding Real Madrid, Barcelona and Bayern Munich, who are among the favourites to win the competition.
It also means the two English sides have the benefit of playing the first leg away from home.
The first legs will be played across February 13/14 and February 20/21 before the second legs on March 5/6 and March 12/13.
Arsenal and Porto were the first two teams drawn out of the hat, with the two clubs facing each other for the first time since the 2009/10 season.
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Porto came out on top in the first leg as 2-1 winners, before the Gunners thumped their Portuguese opponents 5-0 at the Emirates to advance into the quarter-finals.
As for City, they have been paired up with Copenhagen, who beat Manchester United and drew away at Bayern in Group A.
The Citizens were paired with the Danish outfit in the group stage last campaign, where Pep Guardiola‘s men drew away before winning 5-0 at home.
In other standout ties, Napoli will take on Barcelona and Inter Milan pit their wits against Atletico Madrid.
Champions League last-16 draw in full
Porto vs Arsenal
Napoli vs Barcelona
PSG vs Real Sociedad
Inter Milan vs Atletico Madrid
PSV Eindhoven vs Borussia Dortmund
Lazio vs Bayern Munich
Copenhagen vs Manchester City
RB Leipzig vs Real Madrid