Champions League favorite Barcelona and nine-time European champion Real Madrid are among nine former winners in the last-16 draw Thursday.
The bitter rivals are joined by Malaga and Valencia, making Spain the best represented of nine countries with teams in the knockout stage.
Germany has group winners Bayern Munich, Borussia Dortmund and Schalke all seeded in the draw.
England challenges with Manchester United and Arsenal, and Italy has AC Milan and Juventus.
Milan seeks an eighth European title after offseason cost-cutting sales including forward Zlatan Ibrahimovic and defender Thiago Silva to Paris Saint-Germain. An Ibrahimovic reunion could be the most intriguing pairing.
Clubs cannot be drawn against a group-stage opponent, or another from its home country.
First-leg matches are played from Feb. 12-20. Return matches are from March 5-13.