Norwich, without the banned Robbie Brady, may rotate their squad, with Michael McGovern set to start in goal.
Defenders Steven Whittaker and Ryan Bennett, midfielder Alex Pritchard and forwards Josh Murphy and Kyle Lafferty could also feature.
Saints boss Claude Puel is also expected to shuffle his pack and give chances to younger players.
Captain Jose Fonte's transfer request may rule him out. Virgil van Dijk, back from a ban, seems unlikely to play.
MATCH PREVIEW
- This will be the fourth FA Cup tie between Norwich and Southampton, with the Saints winning most recent in the fifth round in February 2003 on their way to the final, where they lost to Arsenal.