| Southampton FC v Levante UD 04/08/2021 | £7.50 | |
| Southampton FC v Athletico Bilbao 07/08/2021 | £7.50 | |
| Southampton FC v Manchester United FC 22/08/2021 | £7.50 | |
| Newport County AFC v Southampton FC 25/08/2021 | £8.50 | |
| Southampton FC v West Ham United FC 11/09/2021 | £7.50 | |
| Manchester City FC v Southampton FC 18/09/2021 | £7.50 | |
| Southampton FC v Wolverhampton Wanderers FC 26/09/2021 | £7.50 | |
| Chelsea FC v Southampton FC 02/10/2021 | £5.99 | |
| Southampton FC v Leeds United FC 16/10/2021 | £7.50 | |
| Southampton FC v Burnley FC 23/10/2021 | £7.50 | |
| Chelsea FC v Southampton FC 26/10/2021 | £7.50 | |
| Southampton FC v Aston Villa FC 05/11/2021 | £7.50 |