Oldham stunned Southend with two quick goals in the second half to secure all three points.
Southend took the lead when James Walker followed in from close range after a cross from Simon Francis.
Chris Taylor produced a superb header to equalise following a right-wing corner from Andy Liddell.
Lee Hughes then got what proved to be the winner when he drilled in a low shot from a tight angle after the home side failed to clear a free-kick.
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Goals: Walker 53.
Oldham: Crossley, Lomax, Stam, Hazell, Jones, Liddell, Allott, Maher, Taylor, Byfield, Hughes. Subs Not Used: Fleming, Gregan, Eardley, Alessandra, Lee.
Booked: Stam, Maher.
Goals: Taylor 67, Hughes 71.
Att: 7,041.
Ref: Phil Crossley (Kent).
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