Southend could be without as many as nine players.
Chris Barker (calf) and Mark Phillips (toe) will be given every opportunity to recover in time but appear set to miss out along with fellow defender Ryan Cresswell, who is suspended.
Midfielder Marc Laird faces three weeks out with a hamstring injury but would have been cup-tied in any case, a ruling which denies Michael Spillane the chance to feature.
Loanee Caolan Lavery has returned to parent club Sheffield Wednesday for treatment after being ruled out for between six to eight weeks with a hamstring injury of his own, with leading scorer Gavin Tomlin (thigh) and midfielder Michael Timlin (broken leg) also absentees.
Boss Paul Sturrock recalled the versatile Bilel Mohsni from exile for Saturday's 2-1 defeat to Northampton but he was sent off in the first half and now starts a three-match ban.
Leyton Orient will have to make two changes to their side.
Left-back Gary Sawyer will miss out after he was stretchered off during Saturday's 2-1 defeat by Hartlepool, with Orient waiting to find out the severity of his knee injury, and striker Charlie MacDonald is cup-tied.
Boss Russell Slade will check on winger Dean Cox after he sat out at the weekend with a thigh problem, while forward Kevin Lisbie is still missing with a hamstring injury.
Slade could hand a full debut to utility man Romain Vincelot, who has made two substitute appearances since joining from Brighton earlier this month.
Nathan Clarke, Leon McSweeney, Jimmy Smith and Anthony Griffith are pushing for recalls as the O's attempt to overturn a 1-0 deficit from the first leg.