| Ajax | 1-0 |  Legia Varsavia | Johan Cruijff Arena | 22 Feb | h. 18:00 |
| APOEL | 2-0 |  Athletic Bilbao | GSP | 22 Feb | h. 18:00 |
Besiktas  | 2-1 |  Hapoel Beer Sheva | Vodafone Park | 22 Feb | h. 18:00 |
FC Copenhagen  | 0-0 |  Ludogorec | Telia Parken | 22 Feb | h. 18:00 |
| Fenerbahce | 1-1 | Krasnodar | Sukru Saracoglu | 22 Feb | h. 18:00 |
| Fiorentina | 2-4 |  Borussia Monchengladbach | Artemio Franchi | 22 Feb | h. 18:00 |
| Genk | 1-0 |  Astra Giurgiu | KRC Genk Arena | 22 Feb | h. 18:00 |
Olympique Lione  | 7-1 | AZ Alkmaar | 22 Feb | h. 18:00 | |
Osmanlispor  | 0-3 |  Olympiakos | Osmanli Stadi | 22 Feb | h. 18:00 |
| Roma | 0-1 | Villarreal | Olimpico | 22 Feb | h. 18:00 |
| Saint Etienne | 0-1 | Manchester United | Stade Geoffroy Guichard | 22 Feb | h. 18:00 |
Schalke 04  | 1-1 |  PAOK | Veltins-Arena | 22 Feb | h. 18:00 |
| Shakhtar Donetsk | 0-2 |  Celta Vigo | Metalist Stadium | 22 Feb | h. 18:00 |
| Sparta Praga | 1-1 |  Rostov | Letná | 22 Feb | h. 18:00 |
Tottenham Hotspur  | 2-2 |  KAA Gent | Wembley Stadium | 22 Feb | h. 18:00 |
| Zenit San Pietroburgo | 3-1 | Anderlecht | Gazprom Arena | 22 Feb | h. 18:00 |