The prize for winning this tie for both of these sides could not be much bigger.
European champions Chelsea await the winner, who will play host to the Premier League outfit.
The bookmakers have League One Brentford as the favourites to win through to round four. Uwe Rosler's side have not been beaten in any of their last six matches in all competitions.
However, in the opening fixture they were pegged back by their League Two visitors, thanks largely to 27-year-old striker Barry Corr.
The Irishman has had a succession of injury problems in recent months but should be passed fit to feature at Griffin Park.
Recent form
Brentford: WWWDDW
Southend: DWWLLL
Possible starting lineups:
Brentford: Moore; Craig, Dean, Logan, Bidwell; Kiernan, Forshaw, Douglas; Donaldson, Trotta, Forrester
Southend: Smith; Clohessy, Cresswell, Phillips, Barker; Timlin, Hurst, Martin; Woodyard, Corr; Tomlin
Sports Mole says: 2-0