The Spanish league leaders will arrive at the Olympic Stadium on the back of a domestic defeat but have won all three of their previous Champions League ties away to Roma.
Runaway Serie A leaders Inter Milan are also in knockout round action on Tuesday when they visit a Liverpool side licking their wounds after a humbling FA Cup home defeat by second tier Barnsley.
The 2-1 loss heaped more pressure on Liverpool boss Rafa Benitez whose side are fifth in the Premier League and in danger of not even competing in the Champions League next season.
Inter rested the strike partnership of Zlatan Ibrahimovic and Julio Cruz at the weekend but both will be back for the club's first meeting with Liverpool since 1965.
Chelsea, boosted by the return of midfielder Frank Lampard and inspirational skipper John Terry, travel to snowbound Athens where they take on Greek survivors Olympiakos Piraeus while German club Schalke play Porto in Gelsenkirchen.