Former champions Chelsea will face Malmo in the last 32 of the Europa League while Arsenal will lock horns again with BATE Borisov.
The two sides met in the Europa League last season, the Gunners hammering the Belarussian side 6-0 at the Emirates.
Five-time champions Sevilla, currently second in La Liga, face a difficult tie against Lazio, beaten finalists in this competition in 1998, who are fifth in Serie A.
The 2004 champions Valencia will have to overcome Celtic if they are to progress to the round of 16 for the first time in three years.
The Scottish side’s coach Brendan Rogers says he has been impressed by the Spanish club in Europe this season after they finished third in a Champions League group including Manchester United and Juventus.