Chelsea have drawn FC Copenhagen, while Arsene Wenger's Arsenal must face Barcelona again in the Champions League round of 16. The Gunners drew 2-2 at home with the Catalan giants in last season's quarter-finals before crashing 4-1 in the return leg.
Tottenham will travel back to the San Siro after being paired with AC Milan.
Spurs topped their group ahead of Inter Milan after a thrilling 4-3 defeat in Italy and a win at White Hart Lane.
Manchester United will take on French side Marseille while Chelsea are up against Danish outfit Copenhagen.
First-leg ties will be played on the 15/16 and 22/23 of February with the second legs scheduled for 8/9 and 15/16 March.
Last 16:
Roma v Shakhtar Donetsk
AC Milan v Tottenham
Valencia v Schalke
Lyon v Real Madrid
Marseille v Manchester United
Copenhagen v Chelsea