Colchester United fell at the first hurdle in the Carling Cup on Tuesday night, as Leyton Orient ran out 2-1 winners at the Weston Homes Community Stadium.
The visitors took an early lead to put the U's on the back foot and grabbed another in the second half to give themselves a cushion.
Whilst the U's created a number of chances inbetween the two goals for the O's, the home team were unable to truly test Glenn Morris until Simon Hackney grabbed a late consolation.
And it will be back to the league this weekend as they look to build on the win over Norwich at the weekend.
The visitors were in front within eighty seconds of the start of the game.
Winger Melligan got the better of Beevers down the wing and sent over a low cross to the far post, which found Patulea rushing in at the far post to bury his header home into the ground and past Cousins.
The visitors then nearly doubled their advantage as Smith snapped up a loose ball on the edge of the box and smashed in a low shot that forced a great save out of Cousins.
The U's looked for a path back into the game, but in a bright start for the visitors, loanee Townsend drove forward to strike in a low shot that forced another good stop out of the home keeper.
The home side were starting to see more of the ball as the half took shape, and a clever ball over the Orient left back sent Lisbie away. He twisted this way and that, eventually contriving space to get into the box before driving a shot into the side netting.
A minute later, and down the other flank, Hackney's trickery and persistence ended with a cross-cum-shot that had Morris scrambling backwards to tip the ball away from under his bar. Unlike on Saturday though, there were no U's players waiting to tuck the ball home.
The home side tried some inventiveness from a free kick on twenty minutes, dropping it short to Perkins who went for a one two on the edge of the box with Platt, before drilling his shot well over the bar.
The U's had found their feet after their early setback, and were first to the loose balls as the half wore on, with a spell of pressure starting to develop as the half hour mark arrived.
Try as they might, though, the U's couldn't quite find their scoring boots. One chance, bang on the half hour mark, saw Perkins break into space towards the box, but slice his effort just wide, with Morris happy to watch it go by the post.
Hackney was proving to be the U's main danger man, seeing plenty of the ball down the left flank and whipping in some balls which more often than not caused danger. One such cross on 33 minutes saw Lisbie heading from distance, but it went wide of the post.
Try as they might, the ball just would not sit for the U's in the box, but they were working hard enough in the final third to ensure that the Orient defenders were never getting a clean clearance out to their more advanced players.
Lisbie went close on 38 minutes, darting in to head a Hackney corner, only to see his effort flash wide of the post.
The U's were then tested at the end of the half as a cross came in down the left hand side and Smith came in at the far post to try and head the ball, only for Okuonghae to clear off the line.
The home team started the second half on the front foot and, three minutes after the restart, Vincent had two bites of the cherry just outside the penalty spot and although it was not the cleanest of strikes, it had Morris turning the ball away for a corner.
The O's were denied a goalscoring chance as Okuonghae denied the hesitating Patulea and that sent the U's away on the counter attack through Vincent. He slotted the ball low to Lisbie who turned his low shot on the angle agonisingly wide of the far post.
The visitors thought they might be in on goal not long afterwards as a long ball saw Townsend and Maybury contest it as it bounced and the wily defender was able to draw a foul, much to the frustration of the home fans.
The U's were on top, though, with Vincent enjoying a running battle with left back Daniels through the early part of the second period.
Mkandawire was the first O's player to go in the book just after the hour mark as he slipped and lost his footing down the left flank and hooked the ball back with his arm to prevent Platt escaping towards goal with the ball.
However, the O's fans were soon celebrating when they doubled their advantage with a fine goal on 63 minutes. The ball was spread out wide to Melligan and, from a narrow angle, he made no mistake as he drilled it across goal and into the far bottom corner past Cousins.
Morris went into the book for kicking the ball away, but the officials decision making was starting to rile the home supporters as the game began to look more difficult for them to get back into.
Platt lifted the home support by winning a corner for which he had no right to get when running to the byline, but the U's were lacking the finesse in the final third that had served them so well three days earlier.
The U's made attacking changes with 20 minutes to go, introducing Hammond and Vernon for Perkins and Beevers as they sought their way back into the match.
And whilst the home team continued to search for that elusive break in front of goal, it just wouldn't go their way.
Cousins had a lucky escape with ten minutes to go when he delayed his clearance from a backpass, which allowed McGleish to get a touch on the ball, only for the U's man to recover.
Hammond came close to getting the U's first of the game as he burst into the box and drilled a shot narrowly over the crossbar, but then overcooked his pass a moment later in a move that ended in typically frustrating fashion for the home team.
The U's captain then had a header cleared off the line from a corner, before the home side were again left disappointed by a ball that wouldn't break in their favour as it entered the penalty area.
Smith joined his team-mates in the book for an elbow in the back of Izzet's head, and the play was all in the U's favour with Orient happy to sit in and defend their advantage into the last five minutes of the match.
That said, they were able to counter attack the U's as a result, but Lisbie was the next to go close as he dropped deep and smacked in a shot that was deflected wide before Hackney's effort from the resulting corner also went wide of the upright.
The frustration boiled over at the end for the U's as Platt saw red for an incident in the penalty area deep into injury time, although many in the ground didn't see what unfolded before the referee made his decision.
The U's gave themselves late hope as Hackney drilled home a free kick from distance but that was literally the last kick of the game as the referee blew up direct from the restart.
Orient continue their cup hoodoo over the U's then, following last season's FA Cup victory, but the U's will return to their league journey on Saturday with a home match against Yeovil Town this weekend.