Scott McGleish wasted two good early chances for the Cobblers - while Darryl Flahavan saved from Lee Williamson.
At the other end, the visitors went close just before the break when Mark Bentley headed Mark Gower's cross straight at Cobblers keeper Lee Harper.
Freddy Eastwood and Luke Guttridge also both headed wide for the Shrimpers, and Flahavan denied Andy Kirk at the death.
Southend boss Steve Tilson:
"I think I'd have taken a 0-0 draw before the game to go back to Roots Hall, so I'm ever so pleased.
"It was always going to be a tough game away from home, as Northampton are a good side and they've come into the play-offs on the back of three wins.
"There weren't too many chances for either side, so it was probably a fair result in the end."
Northampton: Harper, Togwell, Chambers, Willmott, Murray, Low (Sabin 73), Rowson, Hearn, Williamson (Smith 59), McGleish, Kirk.
Subs Not Used: Hunt, Richards, Bunn.
Booked: Willmott, Hearn.
Southend: Flahavan, Jupp, Wilson, Barrett, Prior, Pettefer, Maher, Bentley, Gower (Guttridge 60), Bramble (Dudfield 45), Eastwood (Gray 87).
Subs Not Used: Edwards, Griemink.
Booked: Jupp, Wilson, Bentley.
Ref: L Mason (Lancashire).