Lee Barnard cancelled out a penalty by Oldham's Neal Eardley but Saturday's result was not enough for the Shrimpers, who now have no mathematical chance of finishing in the top six.
Southend had the first chance when Dougie Freedman blazed over but Oldham soon hit the post with a free-kick by midfield man Kevin Maher. Ian Westlake wasted two half-chances before the Latics broke through on 51 minutes following Deane Smalley's charge into the box.
Smalley was dragged down by Peter Clarke, allowing Wales international right-back Eardley to step-up and fire his penalty under keeper Steve Mildenhall.
But Oldham were ahead for less than 10 minutes as they were caught out of position in defence and Theo Robinson set up Barnard, a half-time substitute, to convert from close range.
Southend pushed for a winner and Anthony Grant grazed the crossbar from 25 yards before forcing a save from veteran Oldham keeper Mark Crossley.