Saints have confirmed that Luke Shaw has badly gashed his right knee.
The young left back was stretchered off during the win at Aston Villa after a heavy challenge.
Nigel Adkins was unable to give any timescale for a return but Shaw may face a short spell on the sidelines as a result.
Danny Fox could well be set for a spell in the team to deputise.
Saints are already dealing with injuries to key men Adam Lallana and Jose Fonte while Guly do Prado was unable to figure due to illness.
Gaston Ramirez was also forced off at Villa Park but that was simply cramp.