An even League Two contest hinged on events midway through the second half as Northampton goalkeeper Jordan Archer was shown the red card for fouling Barry Corr in the penalty area.
The Shrimpers striker picked himself to put the spot-kick past substitute Matt Duke and it was damage limitation from that moment on for the Cobblers.
David Worrall made the game safe for the hosts who handed an immediate debut to loan signing JohnJoe O'Toole, signed from Town in midweek.
He played the majority of the game before being replaced by another former Sixfields man in the shape of Gary Deegan.
The result leaves Chris Wilder's side in 15th place in the table on 24 points. They are back in action at home to Plymouth Argyle on 13 December with a free weekend next time out due to their FA Cup exit.
Speaking to BBC Radio Northampton and the official club website after the game, Wilder said: "We wanted a tight game because we felt we could then bring players on for the last 20 minutes who could hurt Southend and win us the game.
"For an away performance I thought we were solid but we could have passed the ball a bit better and we gave away possession too cheaply."