A valiant ten-man Coventry City side came within a whisker of a place in the next round of the Capital One Cup only to have it whipped away by a cruel late winner from Orient's Kevin Lisbie.
Carl Baker gave City a deserved 15th minute lead but goals from Lisbie and Dean Cox overturned the advantage going into the half time interval.
Baker was then given his marching orders ten minutes after the restart following a challenge on Romain Vincelot, leaving City to play the remainder with ten men.
They responded admirably though and grabbed a leveller through Franck Moussa soon after with Leon Clarke's unsuccessful penalty attempt on 78 minutes followed up by Lisbie's 86th minute winner for the hosts.
Boss Steven Pressley kept faith in the side that opened up the club's League One campaign on Saturday with a 1-0 defeat away to Crawley Town
by naming no changes for the clash with the O's.
The Sky Blues then nearly got themselves off to a dream start when, after just two minutes, Callum Wilson chased onto a loose ball down the right and fired a half volleyed cross into the area which Scott Cuthbert nearly diverted into his own net, his blushes only spared by a superb one-handed reaction save from Jamie Jones.
City were by far the more dangerous of the two sides in the opening exchanges as Cyrus Christie twice got down the right to flash in low crosses that Leon Clarke was inches away from connecting with.
A great piece of flair then nearly opened the door again for City after quarter of an hour when a backheel from Clarke found Wilson to loft a first time ball over the back four to Franck Moussa whose shot was saved by the legs of Jones.
The opener was less flair and more route one though as Baker gave the Sky Blues a deserved lead after 22 minutes.
Joe Murphy fired a quick ball up the pitch for Baker who muscled an isolated Gary Sawyer off the ball on the edge of the area and then cut inside the full back before finishing past Jones into the bottom corner.
The lead, however earned, was shortlived though as Lisbie levelled up for Orient four minutes later. Lloyd James whipped in a cross which found Romain Vincelot in the six yard area who connected with the delivery only to be denied by a spectacular save from Murphy. The rebound fell to Kevin Lisbie though who was left with a simple finish to make it 1-1.
It was 2-1 to the hosts 11 minutes later as Cox made the most of a half-clearance from Moses Odubajo's free kick delivery, the ballonly headed as far as Cox who fired low past Murphy from the edge of the area.
City nearly found a leveller of their own on 43 minutes when Moussa rattled the near post with a stinging effort from 20 yards.
Murphy was then required at the other end a minute later to turn Vincelot's header round the post after the midfielder connected with a deep cross from Cox.
The second half was five minutes old when Orient went close to a third, James picking up a ball just inside City's final third and firing a half volley which whistled over Murphy's crossbar.
Jones was required at the other end though three minutes later when Leon Clarke picked up a stray ball 25 yards out and hit it first time only to be denied by the Orient 'keeper with a full-stretch save.
City were dealt a hammer blow after 55 minutes though when Baker was given his marching orders following a 50/50 clash with Vincelot, referee Dean Whitestone brandishing a red card that left the City skipper dismayed.
The City fans may have seen developments on the hour as karma though when Callum Wilson poked a short through ball to Moussa who powered a finish into the roof of the net to level for the Sky Blues.
The goal gave City some momentum and as for the next 18 minutes they dominated proceedings despite being a man down.
That momentum eventually resulted in Leon Clarke winning a penalty with 12 minutes to go, battling with Cuthbert for the ball in the Orient area and drawing a foul off the home skipper, leaving the referee to point to the spot.
Clarke was denied though as his penalty kick was saved by Jones who guessed the right way and trapped the ball under his body, allowing him to scoop it up before Clarke could apply a follow up finish.
And it was a cruel end to the game for the Sky Blues who fought valiantly and were largely the better side the entire time they were a man down.
A deep cross from the left from Moses Odubajo found Lisbie lurking at the back post for the veteran striker to find the net with a diving header four minutes from time.
Attendance: 2,871 (487 Sky Blue Army)
Coventry City: Murphy, Christie, Willis, J Clarke, Adams, Baker (c), Fleck, Thomas, Moussa, L Clarke, Wilson
Subs: Burge (GK), Barton, Daniels, Phillips, Garner, Lobjoit, Maund
Leyton Orient: Jones, Omozusi, Sawyer, Vincelot, Cuthbert (c), Baudry, Cox (Lasimant 84), James, Lisbie, Mooney, Odubajo
Subs: Larkins, Lee, Vanderhyde, Sheraat, Gorman