Britt Assombalonga and Tamika Mkandawire are both unavailable while a number of others will also be assessed.
On-loan pair Assombalonga and Mkandawire both missed the original 1-1 draw between the two sides having been denied permission by parent clubs Watford and Millwall to feature.
And despite returning for the last two games, the duo must again watch from the stands as the Shrimpers return to FA Cup action.
Defender Mark Phillips missed Saturday's goalless draw at Fleetwood due to a knee injury and again sits out, while manager Paul Sturrock is also waiting on other unnamed players who came away at the weekend nursing knocks, with late assessments due to be made.
But there is some good news for Southend with John Spicer and David Martin available after illness and fellow midfielder Michael Timlin also returns having been suspended against The Cod Army.
Bury will be boosted by the return to full fitness of David Healy and captain Steven Schumacher.
Northern Ireland international striker Healy has not played since scoring in his country's 1-1 draw with Azerbaijan due to a calf injury but is set to provide an extra option in attack for boss Kevin Blackwell, who will be without ineligible on-loan Leicester forward Tom Hopper.
Skipper Schumacher came back into the Shakers' midfield ahead of schedule as a second-half substitute during Saturday's 2-0 defeat at home to Leyton Orient following an ankle ligament problem and is pushing for a start.
Aside from Hopper, Bury's five other loanees have been granted permission to take part in cup action by their parent clubs, but it remains to be seen whether the transfer embargo imposed on the Gigg Lane outfit by the Football League will impact upon the availability of Matt Doherty, Zac Thompson, Ethan Ebanks-Landell, Troy Hewitt and Gregg Wylde.
Former Leeds man Ben Parker was prevented from making his debut at the weekend by the embargo having agreed non-contract terms, while fellow defender Phil Picken (knee) remains a long-term absentee.