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| U | Fenerbahçe | - | Lokomotiv Moskou | 2:0 (1:0) | ||
| R | Lokomotiv Moskou | - | Fenerbahçe | 1:1 (1:0) | ||
| U: 16.02.2016 18:00 | R: 25.02.2016 17:00 | Winnaars: Fenerbahçe | ||||
| U | ACF Fiorentina | - | Tottenham Hotspur | 1:1 (0:1) | ||
| R | Tottenham Hotspur | - | ACF Fiorentina | 3:0 (1:0) | ||
| U: 18.02.2016 19:00 | R: 25.02.2016 21:05 | Winnaars: Tottenham Hotspur | ||||
| U | Borussia Dortmund | - | FC Porto | 2:0 (1:0) | ||
| R | FC Porto | - | Borussia Dortmund | 0:1 (0:1) | ||
| U: 18.02.2016 19:00 | R: 25.02.2016 21:05 | Winnaars: Borussia Dortmund | ||||
| U | RSC Anderlecht | - | Olympiakos | 1:0 (0:0) | ||
| R | Olympiakos | - | RSC Anderlecht | 1:2 (1:0, 1:0) n.v. | ||
| U: 18.02.2016 19:00 | R: 25.02.2016 21:05 | Winnaars: RSC Anderlecht | ||||
| U | FC Midtjylland | - | Manchester United | 2:1 (1:1) | ||
| R | Manchester United | - | FC Midtjylland | 5:1 (1:1) | ||
| U: 18.02.2016 19:00 | R: 25.02.2016 21:05 | Winnaars: Manchester United | ||||
| U | Sevilla FC | - | Molde FK | 3:0 (1:0) | ||
| R | Molde FK | - | Sevilla FC | 1:0 (1:0) | ||
| U: 18.02.2016 19:00 | R: 25.02.2016 21:05 | Winnaars: Sevilla FC | ||||
| U | Villarreal CF | - | SSC Napoli | 1:0 (0:0) | ||
| R | SSC Napoli | - | Villarreal CF | 1:1 (1:0) | ||
| U: 18.02.2016 19:00 | R: 25.02.2016 21:05 | Winnaars: Villarreal CF | ||||
| U | AS Saint-Étienne | - | FC Basel 1893 | 3:2 (2:1) | ||
| R | FC Basel 1893 | - | AS Saint-Étienne | 2:1 (1:0) | ||
| U: 18.02.2016 19:00 | R: 25.02.2016 21:05 | Winnaars: FC Basel 1893 | ||||
| U | Valencia CF | - | Rapid Wien | 6:0 (5:0) | ||
| R | Rapid Wien | - | Valencia CF | 0:4 (0:0) | ||
| U: 18.02.2016 21:05 | R: 25.02.2016 19:00 | Winnaars: Valencia CF | ||||
| U | FC Augsburg | - | Liverpool FC | 0:0 (0:0) | ||
| R | Liverpool FC | - | FC Augsburg | 1:0 (1:0) | ||
| U: 18.02.2016 21:05 | R: 25.02.2016 19:00 | Winnaars: Liverpool FC | ||||
| U | Sparta Praag | - | FK Krasnodar | 1:0 (0:0) | ||
| R | FK Krasnodar | - | Sparta Praag | 0:3 (0:0) | ||
| U: 18.02.2016 21:05 | R: 25.02.2016 19:00 | Winnaars: Sparta Praag | ||||
| U | Galatasaray | - | Lazio | 1:1 (1:1) | ||
| R | Lazio | - | Galatasaray | 3:1 (0:0) | ||
| U: 18.02.2016 21:05 | R: 25.02.2016 19:00 | Winnaars: Lazio | ||||
| U | FC Sion | - | Sporting Braga | 1:2 (0:1) | ||
| R | Sporting Braga | - | FC Sion | 2:2 (1:2) | ||
| U: 18.02.2016 21:05 | R: 24.02.2016 18:00 | Winnaars: Sporting Braga | ||||
| U | Shakhtar Donetsk | - | FC Schalke 04 | 0:0 (0:0) | ||
| R | FC Schalke 04 | - | Shakhtar Donetsk | 0:3 (0:1) | ||
| U: 18.02.2016 21:05 | R: 25.02.2016 19:00 | Winnaars: Shakhtar Donetsk | ||||
| U | Olympique Marseille | - | Athletic Club | 0:1 (0:0) | ||
| R | Athletic Club | - | Olympique Marseille | 1:1 (0:1) | ||
| U: 18.02.2016 21:05 | R: 25.02.2016 19:00 | Winnaars: Athletic Club | ||||
| U | Sporting CP | - | Bayer Leverkusen | 0:1 (0:1) | ||
| R | Bayer Leverkusen | - | Sporting CP | 3:1 (1:1) | ||
| U: 18.02.2016 21:05 | R: 25.02.2016 19:00 | Winnaars: Bayer Leverkusen | ||||
