| Local | Visita | Hora | |
|---|---|---|---|
| Viernes 22 de Octubre | |||
| Durango | 2 - 0 | Tecos | 20:00 |
| Torino | 3 - 2 | Genoa | 11:30 |
| FSV Mainz 05 | 4 - 1 | FC Augsburg | 13:30 |
| Alessandria | 1 - 0 | Crotone | 13:30 |
| Sampdoria | 2 - 1 | Spezia | 13:45 |
| Arsenal | 3 - 1 | Aston Villa | 14:00 |
| Guimaraes | 2 - 1 | Marítimo | 14:15 |
| Willem II | 1 - 1 | Fortuna Sittard | 13:00 |
| Osasuna | 1 - 1 | Granada CF | 14:00 |
| SC Paderborn 07 | 1 - 2 | Hamburger SV | 11:30 |
| Saint Etienne | 2 - 2 | Angers | 14:00 |
| FC Eindhoven | 1 - 3 | Jong Ajax | 13:00 |
| Jong AZ | 0 - 1 | FC Volendam | 13:00 |
| Almere City FC | 3 - 5 | Jong PSV | 13:00 |
| ADO Den Haag | 0 - 2 | Excelsior | 13:00 |
| VVV Venlo | 1 - 2 | De Graafschap | 13:00 |
| NAC Breda | 3 - 0 | MVV | 13:00 |
| Eibar | 2 - 1 | FC Cartagena | 14:00 |
| Mazatlán | 2 - 1 | Club Queretaro | 21:00 |
| Academia Cantolao | 2 - 0 | UTC | 11:00 |
| Ayacucho FC | 1 - 3 | Cienciano | 13:15 |
| Sport Boys | 3 - 3 | Carlos A. Mannucci | 15:30 |
| Tecnico Universitario | 1 - 1 | Aucas | 19:00 |
| Club Atlético Güemes | 3 - 0 | Santamarina | 15:10 |
| Independ. Rivadavia | 3 - 2 | Atletico DE Rafaela | 19:10 |
| Avai | 1 - 0 | Cruzeiro | 19:30 |
| 3 de Febrero | 1 - 4 | General Caballero | 15:00 |
| Jaguares | 1 - 1 | Envigado | 17:00 |
| Quindio | 1 - 0 | Alianza Petrolera | 19:00 |
