The South Coast club will travel to Anfield for the first league tie after November's international break on Saturday. According to the Liverpool Echo, the centre-back's chances of facing Mauricio Pellegrino has been hampered due to a thigh problem.
Matip is unlikely to be risked when Southampton visit Merseyside on 18 November. The German central defender's injury setback will force Jurgen Klopp to make late changes for Saturday's league clash against Southampton.
Apart from the ex-Schalke defender, the former Borussia Dortmund manager has the services of compatriot Ragnar Klavan and Dejan Lovren as the first choice centre-backs in the squad. Versatile defender Joe Gomez can also feature in the heart of the back four.
The Liverpool Echo report claims Klopp is likely to hand Lovren a first start for the Reds since his horror show against Tottenham Hotspur in October. The German manager saw his side suffer a 4-1 defeat at Wembley, conceding two early goals.
Klopp did not hold back in criticising the former Southampton man, who was withdrawn in the 31st minute against Tottenham. Matip's injury blow could force Liverpool manager to start the Croatian international in the heart of the defence alongside Klavan.
The 26-year-old German defender's injury is likely to disappoint Klopp, who was handed an injury boost following the return of several players this week. There was concern over Sadio Mane's fitness for the clash against his former club owing to a slight recurrence in his old hamstring injury while on international duty with Senegal.
The African nation sent Mane back to Liverpool and the forward has declared himself fit after returning to full training.
Liverpool boss has confirmed a decision will be taken on Mane, while adding that Adam Lallana will feature for the first time this season on Saturday. Club captain Jordan Henderson has also returned to full training. In addition to this, Philippe Coutinho is set to start, having missed the last three matches due to a groin injury.