Jonathan Forte hit the post for the visitors, who are six points above the bottom four, before Tareiq Holmes-Dennis sent an effort wide.
Oldham keeper Joel Coleman saved a David Worrall shot at the other end.
Main fired home after the hour mark as he latched on to Forte's pass to seal victory for the Latics.
Oldham have a sizeable cushion above the League One relegation places with three games left to play, while Southend remain in 13th place.
Oldham Athletic boosted their hopes of League One survival as Curtis Main's second-half goal sealed a vital three points against Southend United.