The Lions captain, who was ruled out of last Saturday's away victory at Barnsley, also looks likely to miss Tuesday's home league match against Watford. Midfielder Liam Trotter is set to retain the captain's armband for the visit of the Saints to The Den on Saturday.
Boss Kenny Jackett is still without defensive duo Alan Dunne and Shane Lowry, who are both unavailable through suspension. The pair are to serve the last of their three-match bans after their dismissals a fortnight ago against Birmingham City.
Winger Hamer Bouazza is expected to shake off a groin injury picked up last weekend as Millwall prepare to name an unchanged side. Striker Shaun Batt should be named among the substitutes as he continues his return to full fitness.
Long-term absentees Therry Racon and Tamika Mkandawire are continuing their recovery from ankle and knee injuries respectively.
Southampton are boosted by the return of leading marksman Rickie Lambert following the completion of his three-match suspension. New Signing Tadanari Lee could also be involved provided international clearance is received in time following his move from Sanfrecce Hiroshima.
One-time Millwall loanee Jason Puncheon could be included in Southampton's match-day squad. As NewsatDen reported earlier in the week, the winger has returned to the first-team picture at St. Mary's and may make his return against the Lions.
The Saints will, however, be without the cup-tied Iago Falque, while Adam Lallana and Jos Hooiveld are both doubts with groin and hamstring problems.