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Jay Emmanuel-Thomas claimed a goal and an assist as Gills got their season off to a winning start.
They came back from a goal down to win the game infront of over 1,700 travelling fans.
Emmanuel-Thomas equalised for the Gills late in the first half after Stephen McLaughlin had put Southend ahead.
Max Ehmer headed Gillingham ahead soon after the restart and Emmanuel Osadebe started and ended a move to make it 3-1.
Striker Emmanuel-Thomas signed in time, on loan from QPR, to make his debut at Southend, lining up to partner Cody McDonald in attack.
Osadebe, who spent the summer playing in central defence, was the surprise pick in midfield, getting in ahead of new signing Billy Knott and Jake Hessenthaler.
Southend included former Gills winger Jermaine McGlashan in their starting XI along with title winning captain Adam Barrett. McGlashan was kept quiet all match.
Gillingham, in their familiar 4-4-2 set-up, struggled to settle in the first half but ended it on level terms thanks to a classy strike from their new man.
But the best of the first half efforts fell Southend’s way. Simon Cox put a great chance wide, screwing a shot past the post after fellow striker David Mooney pulled the ball back.
Paul Konchesky had arrived just at the right time to clear early on and also won a header from McLaughline’s free-kick.
McDonald headed a good chance wide for the Gills and with 23 minutes gone it was the home side who went ahead. The ball was played through Gills’ midfield and McLaughlin tried his luck from 25 yards, with the ball squirming under Nelson and into the net.
Nelson was called upon moment later to make a great save from Mooney, spreading himself well to deny the Southend striker after he found himself with a free header.
Gillingham levelled with seven minutes of the half remaining. A corner from Konchesky was played low to Emmanuel-Thomas and the QPR loan striker fired in through a crowd.
The Gills took the lead just two minutes after the restart when a throw from Ryan Jackson was flicked on by Ehmer and the header had just enough on it to beat keeper Mark Oxley.
Gillingham kept the pressure on Southend, with McDonald and Emmanuel-Thomas both going close with shots.
Rory Donnelly, on for McDonald, almost capitalised on a mix-up between Barrett and keeper Oxley but the view to goal was blocked.
With just over 10 minutes left the Gills added a third, shortly after Southend had sacrificed a defender in a bid to get back into the game. Osadebe broke forward from midfield and Emmanuel-Thomas laid the ball off for the midfielder to finish in the bottom corner.
Southend: Oxley, Demetriou (King 78mins), Barrett, Thompson, Coker, McGlashan, Leonard, Atkinson, McLaughlin (O’Neill 85mins), Cox, Mooney (Williams 68mins). Subs not used: White, Sokolik, Bridge, Smith.
Gillingham: Nelson, Jackson, Konchesky, Ehmer, Oshilaja, Wright, Byrne, Osadebe (Knott 90mins), Dack, McDonald, Emmanuel-Thomas (Quigley 86mins). Subs not used: Hadler, Hessenthaler, Donnelly, Oldaker, Dickenson.
Attendance: 8,141 (1,769 away)