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| Thursday 18 February 2016 |
| Fiorentina | v | Tottenham Hotspur | Artemio Franchi | 20:00 | |
| St Etienne | v | FC Basel | Stade Geoffroy-Guichard | 20:00 | |
| RSC Anderlecht | v | Olympiakos | Constant Vanden Stockstadion | 20:00 | |
| Borussia Dortmund | v | FC Porto | Signal Iduna Park | 20:00 | |
| Sevilla | v | Molde | Ramon-Sanchez Pizjuan | 20:00 | |
| FC Midtjylland | v | Manchester United | MCH Arena | 20:00 | |
| Villarreal | v | Napoli | El Madrigal | 20:00 | |
| Sporting Lisbon | v | Bayer 04 Leverkusen | Estadio Jose Alvalade | 22:05 | |
| Galatasaray | v | Lazio | Turk Telekom Arena | 22:05 | |
| Marseille | v | Athletic Club | Stade Velodrome | 22:05 | |
| Shakhtar Donetsk | v | FC Schalke 04 | Arena Lviv | 22:05 | |
| Valencia CF | v | SK Rapid Wien | Mestalla | 22:05 | |
| FC Augsburg | v | Liverpool | WWK ARENA | 22:05 | |
| FC Sion | v | Sporting Braga | Stade Tourbillon | 22:05 | |
| Sparta Prague | v | FK Krasnodar | Generali Arena | 22:05 |
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