Cedric Soares, Jannik Vestergaard and Shane Long will all miss Southampton's FA Cup fourth-round tie against Tottenham.
Full-back Soares is expected to be out for around three weeks with knee ligament damage suffered in the midweek win at Crystal Palace, while centre-back Vestergaard (concussion) and forward Long (knee) also picked up problems at Selhurst Park.
The enforced absence of Portugal international Soares could see midfielder James Ward-Prowse deployed at right-back, with Kevin Danso another option.
Saints boss Ralph Hasenhuttl plans to make some changes for the all-Premier League tie. Jan Bednarek is expected to be available after missing out against Palace with an Achilles issue, but fellow defender Yan Valery remains sidelined due to a viral infection.
Tottenham will be without Harry Winks for the trip to the south coast.
The midfielder picked up an ankle injury in the midweek win over Norwich and is set for several weeks on the sidelines.
Gedson Fernandes and Tanguy Ndombele will be hoping for starts at St Mary's Stadium, while Christian Eriksen's future is in the air as he closes in on a move to Inter Milan.
Harry Kane (hamstring), Moussa Sissoko (knee) and Ben Davies (ankle) continue their recovery.