The Mariners started the game well with a goal from John-Lewis, but Brown levelled for the home side with a fantastic strike from 20 yards, then a mix up in the Town defence allowed Southport to score against the run of play and bag the 3 points.
Injuries to Clayton McDonald and Joe Colbeck added to Town’s misery.
Paul Hurst made one change from the side that drew 1-1 with Cambridge United at the weekend, with Joe Colbeck coming in for Alex Rodman in the Town midfield.
The Mariners took the lead on 8 minutes after some good persistent play down the right-hand side, with ROSS HANNAH’S clever lob finding John Lewis to make it 1-0.
Osawe, on the edge of the six yard box, should have levelled things on 15 minutes but his effort was wide.
Southport were now having a lot of possession without causing the Mariners too much concern.
But the home side were level on 35 minutes. Southport broke away down the Town right and they looked to have been halted by a good tackle from Clayton McDonald. But the ball broke nicely for BROWN who drilled a low shot past McKeown and into the net.
Minutes later Ross Hannah latched onto a great through ball from John Lewis, but his placed effort hit the inside of the post and was cleared.
Andi Thanoj replaced Scott Kerr at half time.
Southport started the second half well with McKeown parrying a shot from Brown and then McDonald threw himself in the way of another effort to keep the Sandgrounders at bay.
It was bad news for Town on 52 minutes when Clayton McDonald appeared to go down with a hamstring problem. The Mariners had do reshuffle the defence with Sam Hatton coming on to replace Fyfield at left-back, and former York City man Fyfield joining Shaun Pearson at the heart of the defence.
Shaun Pearson almost restored Town’s lead on 52 minutes when his overhead kick hit the post and was cleared by the Southport defence.
Disaster struck for the Mariners on 67 minutes when a mix up in the Town defence allowed OSAWE in to make it 2-1.
The goal was harsh on Town and totally against the run of play.
And things went from bad to worse for Town when Joe Colbeck limped off.
Ross Hannah had a chance to get back into the game but his free-kick failed to trouble the Southport keeper and went wide.
The Mariners were having a lot of possession but struggled to create clear cut chances.
Shaun Pearson looked to have grabbed the equaliser for Town in stoppage time when he got on the end of a great ball from Thanoj but his powerful header grazed the top of the crossbar.