All kick-off times in GMT.
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- Sun, Nov 18, 2012
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| FT | Deportivo La Coruña | 0 - 2 | Levante |
| FT | Celta Vigo | 1 - 1 | Mallorca |
| FT | Getafe | 2 - 1 | Real Valladolid |
| FT | Granada | 0 - 1 | Atletico Madrid |
| FT | Sevilla FC | 5 - 1 | Real Betis |
| FT | Cordoba | 1 - 2 | Hercules |
| FT | Elche | 1 - 0 | AD Alcorcon |
| FT | Recreativo Huelva | 2 - 5 | CD Sabadell |
| FT | Huesca | 2 - 1 | Guadalajara |
| FT | Mirandes | 0 - 0 | Real Madrid Castilla |
| FT | Numancia | 0 - 0 | Almeria |
| FT | Bologna | 3 - 0 | Palermo |
| FT | Catania | 2 - 1 | Chievo Verona |
| FT | Fiorentina | 4 - 1 | Atalanta |
| FT | Internazionale | 2 - 2 | Cagliari |
| FT | Siena | 1 - 0 | US Pescara |
| FT | Udinese | 2 - 2 | Parma |
| FT | Sampdoria | 3 - 1 | Genoa |
| FT | MSV Duisburg | 2 - 1 | FC Erzgebirge Aue |
| FT | SSV Jahn Regensburg | 3 - 3 | FC Union Berlin |
| FT | VfL Bochum | 5 - 2 | SV Sandhausen |
| FT | Vitesse Arnhem | 4 - 1 | NEC Nijmegen |
| FT | FC Utrecht | 1 - 1 | Twente Enschede |
| FT | Feyenoord Rotterdam | 3 - 0 | Willem II Tilburg |
| FT | SC Heracles Almelo | 5 - 1 | Roda JC Kerkrade |
| FT | CSKA Moscow | 3 - 0 | FK Amkar Perm' |
| FT | Mordovia Saransk | 0 - 3 | Kuban Krasnodar |
| FT | Anzhi Makhachkala | 0 - 0 | FK Rostov-Na-Donu |
| FT | Akhisar Belediye | 0 - 2 | Kasimpasa |
| FT | Kayserispor | 1 - 1 | Gaziantepspor |
| FT | Antalyaspor | 3 - 5 | Besiktas |
| FT | Bursaspor | 3 - 0 | Mersin Idmanyurdu |
| FT | OFI Crete | 0 - 2 | Levadiakos |
| FT | FC Xanthi | 0 - 0 | Panthrakikos |
| FT | Veria | 0 - 4 | AEK Athens |
| FT | Panathinaikos | 2 - 0 | PAOK Salonika |
| FT | Arsenal de Sarandí | 3 - 0 | Godoy Cruz de Mendoza |
| FT | Colón de Santa Fe | 2 - 0 | Unión de Santa Fe |
| FT | San Martín de San Juan | 2 - 2 | Tigre |
| FT | Newell's Old Boys | 1 - 2 | All Boys |
| FT | Vélez Sarsfield | 0 - 1 | Boca Juniors |
| Group A | |||
|---|---|---|---|
| FT | Club Sportivo Cienciano | 2 - 0 | José Gálvez |
| FT | Cobresol | 1 - 2 | San Martin |
| FT | Universitario de Deportes | 0 - 3 | Sporting Cristal |
| Group B | |||
| FT | Alianza Lima | 2 - 0 | Real Garcilaso |
| FT | César Vallejo | 1 - 0 | Melgar FBC |
| FT | Sport Boys | 1 - 2 | Juan Aurich |
| FT | Unión Comercio | 2 - 0 | León de Huánuco |
| FT | Deportivo Quito | 0 - 2 | Barcelona |
| FT | Olmedo | 0 - 2 | Club Deportivo Cuenca |
| FT | Independiente Terán | 1 - 0 | LDU Quito |
| FT | Manta F.C. | 4 - 0 | Tec. Universitario |
| FT | Emelec | 2 - 1 | El Nacional |
| FT | Atlético Venezuela | 0 - 4 | Trujillanos |
| FT | Atlético Vigía | 1 - 0 | Dep. Petare |
| FT | Portuguesa | 2 - 0 | Monagas SC |
| FT | Anzoátegui | 3 - 2 | Deportivo Táchira |
| FT | Caracas F.C. | 4 - 1 | Llaneros |
| FT | CD Lara | 1 - 0 | Yaracuyanos |
| FT | Zamora | 3 - 0 | A.C. Mineros |
| FT | Belen | 0 - 0 | Herediano |
| FT | Cartagines | 0 - 1 | Club Sport Uruguay |
| FT | Santos | 2 - 2 | Saprissa |
| FT | Limon | 2 - 1 | Perez Zeledon |
| FT | Alajuelense | 3 - 1 | Puntarenas |
| FT | San Carlos | 0 - 2 | Carmelita |