Jevani Brown's shone for Colchester United with a hat-trick in a 6-1 win for the U's. Michael Folivi, Noah Chilvers and Kwame Poku were also on the score sheet as Steve Ball's side smash Essex rivals in the Papa John's Trophy.
Steve Ball made five changes from the side that exited the FA Cup in the first round at home to Marine, with George, Scarlett, Clampin, Bohui and Folivi all coming into the starting eleven.
Ryan Clampin was back in the team for the first time this season, with Josh Bohui and Michael Folivi both handed starts against Southend United.
Colchester United looked to get ahead early and had tested Seaden twice in the opeing seven minutes. The visiting 'keeper was forced to deny Chilvers from a low cross before pulling off a brilliant save to deny Jevani Brown who was on-on-one.
Harry Seaden was beaten after eight minutes, but Shaun Hobson was covering his man, and turned the goal-bound ball away in to an attack for the Shrimpers. Shamal George was called into action as he made up for his initial mistake of gifting the ball back to Southend when he denied Sterling with a fine diving save.
And the exhilertaing opening ten minutes was capped off with Josh Bohui striking the woodwork. His looping effort rattled the bar, with Seaden beaten.
But it only took five more minutes for the U's to get their noses in front, when Jevani Brown headed home after quarter of a hour had been played. Brown bagged his fourth in three games when he jumped highest against two Southend defenders to guide the ball into the far corner and out of reach of Harry Seaden.
Southend then piled the pressure on George's goal with high pressure and pressing the ball constantly. The U's 'keeper was forced in to a save when Sterling ran through before pulling the trigger, but George got his body behind the ball and parried away.
But Steve Ball's side quickly put themselves back in command of the game. Kwame Poku tested Seaden with a curling effort that was bending towards the near top corner, before Jevani Brown scored his second of the game.
Michael Folivi did well to nick the ball away from the Shrimpers before a fine through ball from Pell was perfectly controlled and dispatched over Seaden by Brown to double his goal tally and the U's lead in the game.
Southend rallied again to try and get a goal back before the break with a series of corners and free kicks tossed in towards Sowunmi and Eastman, but the home centre backs were able to deal with each cross and maintain their team's two-goal advantage at half time.
Just thirty seconds in to the second half, Jevani Brown was unlucky not to have his second hat-trick in three games when he saw his low right-footed effort saved by Seaden after a neat through ball from Chilvers.
But Brown didn't have to wait long to get his second hat-trick in seven days. Josh Bohui was brought down in area by Shaun Hobson, with Brown stepping up to send Seaden the wrong way and get his third of the evening.
It took all of five further minutes for the U's to increase their lead, with Michael Folivi getting his first goal on his first start for Colchester United. After running through, he powered the ball home, with the visiting 'keeper getting a hand to it but unable to keep out the shot.
Samson Tovide was unlucky not to open his Colchester United account when he smashed the ball against the bar with a dipping twenty-five yard effort, before Noah Chilvers capitalised on the poor defending from Southend to add a fifth with a low driven effort.
And the U's kept piling the misery on Mark Molsley's side when Poku slid in a sixth with seven minutes left to play. He arrived late at the back post to roll the ball beyond Seaden.
But the U's were unable to keep the clean sheet that they wanted so badly when Sterling was found unmarked before slotting home past George.
The consolation didn't take any shine off the U's wonderful performance though, as the bounced back with a much needed confidence boost after Saturday's defeat.
Next up for Colchester United is a home game back in the league with Leyton Orient coming to the JCS on Saturday.
Colchester United starting XI: George, Sowunmi, Pell (Marshall Miranda 58'), Brown (Tovide 58'), Chilvers, Scarlett, Eastman (Welch-Hayes 63'), Clampin, Poku, Bohui, Folivi.
Unused subs: Coulter, Senior, Cowan-Hall, Sayer.
Southend United starting XI: Seaden, Hobson, Goodship (Nathaniel-George 46'), Egbri, Clifford, Phillips, Sterling, Acquah (Coker 71'), Rush, Taylor, White (Chandler 46').
Unused subs: Grossart, Davis, Adedoja, Brown.