| Lineups found Starting lineup changes since last game |
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| July 2021 |
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| Coach Nuno Espírito Santo since 30-Jun-21 |
| August 2021 |
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| Coach Cathro since 03-Jul-21 |
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 07-Aug to 14-Aug Romero, Cristian (1998) Knee Injury |
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| 08-Aug to 18-Aug Sessegnon, R Hamstring Strain |
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| 08-Aug to 19-Aug Kane Knock |
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| 08-Aug to 10-Sep Ndombèlé Knock |
| September 2021 |
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| 27-Aug to 28-Aug Son, Heung-min Thigh Injury |
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| 29-Aug to 11-Sep Bergwijn Ankle Injury |
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| 30-Aug to 20-Nov Sessegnon, R Knock |
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| 30-Aug to 18-Sep Son, Heung-min Tight Calf Muscles |
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| 30-Aug to 10-Sep Skipp Groin Injury |
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 06-Sep to 18-Sep Romero, Cristian (1998) Quarantine Regulations |
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| 06-Sep to 18-Sep Lo Celso Quarantine Regulations |
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| 06-Sep to 18-Sep Sánchez, Davinson Quarantine Regulations |
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| 11-Sep to 18-Sep Dier Thigh Injury |
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| 16-Sep to 16-Oct Bergwijn Ankle Injury |
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| 17-Sep to 19-Sep Tanganga Domestic Red Card Ban |
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| 17-Sep to 25-Sep Lucas Moura Ankle Injury |
| M.3 | 22-Sep | away | Wolves | | 2-2 | 4-3-3 | |
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| October 2021 |
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| 27-Sep to 16-Oct Davies, Ben (1993) Illness |
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| 10-Oct to 26-Oct Doherty, Matthew (1992) Knock |
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| 27-Oct to 20-Nov Bryan Gil Hamstring Injury |
| M.4 | 27-Oct | away | Burnley | | 0-1 | 4-2-3-1 | In:E Royal, Hojb'g, Bergwijn, Out:Tanganga, Alli, Ndom'le, |
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| December 2021 |
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| Coach Conte since 02-Nov-21 |
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| Coach Stellini since 02-Nov-21 |
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| 18-Dec to 24-Jan Romero, Cristian (1998) Thigh Injury |
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| 18-Dec to 29-Dec Scarlett, D Illness |
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| 18-Dec to 20-Dec Bryan Gil Illness |
| M.5 | 22-Dec | | West Ham | | 2-1 | 3-4-2-1 | In:Lloris, Dier, Doherty, Reguilón, L Moura, Out:Gollini, E Royal, Romero, B Gil, L Celso, |
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| January 2022 |
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| 25-Dec to 02-Jan Sessegnon, R Thigh Injury |
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| 27-Dec to 29-Dec Lo Celso Injury |
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| 31-Dec to 02-Jan Bergwijn Calf Injury |
| M.6 | 05-Jan | away | Chelsea | | 2-0 | 3-4-3 | In:Tanganga, E Royal, Son, Out:Dier, Reguilón, Bergwijn, |
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| M.7 | 12-Jan | | Chelsea | | 0-1 | 5-3-2 | In:Gollini, L Celso, Winks, Out:Lloris, Skipp, Son, |
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| 15-Jan to 17-Jan Reguilón Muscle Injury |
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| 15-Jan to 20-Jan Dier Illness |
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| 15-Jan to 24-Jan Son, Heung-min Muscle Injury |
| February 2022 |
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| 23-Jan to 01-Jun Tanganga Knee Injury |
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| 24-Jan to 14-Feb Dier Thigh Injury |
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| 24-Jan to 23-May Skipp Groin Strain |
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| 15-Feb to 21-Feb Reguilón Illness |
| Color References: GK, DF, DM, MF, FW , Unknown Pos |