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A strong Gillingham team were beaten 3-0 in their first Final Third Development League match of the season.
The Gills had the better of the early exchanges but Southend’s Jason Williams bagged an 18-minute hat-trick.
Gillingham included a number of senior players who have just returned from injury.
Cody McDonad, Doug Loft and Emmanuel Osadebe all started the match, giving them valuable time on the pitch ahead of Saturday's league match.
Jermaine McGlashan and Max Ehmer were also starters for the Gills in Wednesday afternoon’s game at Beechings Cross, as was striker Ben Williamson.
The home side had a number of first half efforts, with Elliott List firing over within the first minute and having another saved by the keeper.
Loft also had a long-range effort saved. Ehmer had a header cleared off the line early in the second half but Williams netted the opener for Southend on 57 minutes.
He doubled the lead six minutes later and had a free header from a corner to make it 3-0 and complete his hat-trick.
Williamson struck the bar for the Gills with two minutes left and List’s follow-up was cleared.
Gillingham: Hadler, Emptage, Dickenson, Davies, Ehmer, Mcglashan, Osadebe, Loft, List, McDonald, Williamson