Leyton Orient 1 Carlisle United 0: Carlisle's promotion hopes suffered another blow as Jon Mellish's own-goal sent them to defeat against the leaders.
Mellish inadvertently deflected a Ruel Sotiriou drive past Tomas Holy in the 73rd minute in east London.
The defender then blew a great chance to equalise late on after rounding home keeper Lawrence Vigouroux, but failed to finish into an empty net.
It meant a fourth game without a win or a goal for Carlisle, in front of a big 1,177-strong travelling support.
They remain fourth in the table, but rivals such as Bradford City are making up ground in the race - whilst the Blues also suffered a double injury blow.
They lost both Morgan Feeney and the returning Fin Back to hamstring injuries in the first half on a damaging afternoon at the Breyer Group Stadium.
Orient, meanwhile, had Charlie Kelman sent off in the second half but Carlisle couldn't punish the ten men.
They applied late pressure but were short of chances, other than Mellish's sitter.
Simpson made four changes to his side, with fit-again Paul Huntington and Back - making his first appearance since November - joined by Kristian Dennis and Alfie McCalmont in the XI.
Making way were Joel Senior and JK Gordon - both out of the squad - along with Ben Barclay and Joe Garner, while Jamie Devitt came into the 18 among the substitutes.
Orient boss Richie Wellens made three changes, with Kieran Sadlier, Rob Hunt and Kelman taking the places of Aaron Drinan, Jordan Brown and Sotiriou.
An evenly-contested first half then played out - but one which saw the Blues suffer those two injury blows.
The match was only seven minutes old when Feeney, after competing for a ball near the Orient box, stayed down and could not continue.
Barclay took his place in defence, as Carlisle looked to unsettle Orient with some good pressing in the home half.
They created an opening on ten minutes when Back and the busy McCalmont combined, Dennis' resulting flick saved by keeper Vigouroux.
Orient looked for dangerman Paul Smyth on the right and United had to be watchful to keep out a searching cross from the home number seven midway through the half.
A real opportunity then came United's way on 28 minutes when McCalmont and Back combined neatly again, but Back delayed his cut-back to Owen Moxon, who was in space in the box, and could only win a corner.
Orient put pressure on Carlisle through the running of Sadlier and Kelman but clear-cut chances remained scarce.
Leyton Orient v Carlisle United - as it happened
United then suffered the sad sight of Back going down, the loanee looking extremely disconsolate as he was eventually helped to his feet after treatment, going off to be replaced by Jordan Gibson - Simpson later saying the Nottingham Forest loanee had hurt the different leg to the one he damaged last November.
The hosts were denied a penalty after handball appeals against Callum Guy, while Rob Hunt swept a shot over the bar.
Carlisle's pressing continued to give them hope of hurting the Os, and a foul on Moxon led to a free-kick which Gibson curled just wide.
In first-half added time, a dangerous run by Orient's Jayden Sweeney forced chances for Smyth and Sadlier but things were finely poised at 0-0 come the interval.
The hosts made a change at the break, captain Darren Pratley replaced by Jordan Brown, before a Dennis interception allowed the Blues to break, but Jack Armer's cross from a dangerous position was cut out.
At the other end, a low Sadlier finish was saved by Holy, who smothered the ball before Kelman could attack the rebound.
Moxon fired a free-kick too high for Carlisle before keeper Holy made a vital, diving save to keep out George Moncur's goalbound effort following a Smyth run.
Another big penalty appeal followed as Huntington slid in on Smyth but ref Ben Speedie only awarded the hosts a corner.
Simpson made a triple change midway through the half with Garner, Ryan Edmondson and Jack Robinson replacing Dennis, Patrick and McCalmont.
Smyth rifled just wide of the near post as the hosts looked for an opener - and then they got one in fortunate circumstances.
Sub Sotiriou was the creator as he cut in from the left, and the low drive across the box deflected twice and, as it struck Mellish, the ball spun agonisingly past the wrongfooted Holy and into the bottom left corner.
Carlisle now had to up their attacking game, having created very little - and were up against ten men for the last 15 minutes, after Kelman's late challenge on Mellish saw a second yellow card and his dismissal.
The hosts made a double change as they looked to close things out, but Carlisle then forced a golden chance to level as they kept things alive outside the Orient box before Mellish burst through.
He rounded Vigouroux and looked set to slot into an empty net...but his finish was weak and allowed Beckles to clear.
Carlisle forced further corners, Edmondson heading one of them over the bar, with Gibson denied by Vigouroux after a late free-kick routine.
But the Blues' inability to create anything more clear-cut cost them as they went down to a second successive defeat on the road.
Orient: Vigouroux, Hunt, Beckles, Sweeney, Turns, Pratley (Brown 46), El Mizouni, Moncur (Drinan 79), Kelman, Sadlier (Sotiriou 71), Smyth (Lyden 79). Not used: Sargeant, James, McCart.
Goal: Mellish 73og
Booked: Kelman, Pratley, Beckles, Vigouroux. Sent off: Kelman.
United: Holy, Feeney (Barclay 7), Huntington, Mellish, Back (Gibson 39), Armer, Guy, Moxon, McCalmont (Robinson 67), Patrick (Edmondson 67), Dennis (Garner 67). Not used: Kelly, Devitt.
Booked: Dennis, Armer.
Ref: Benjamin Speedie.
Crowd: 8,713 (1,177 United fans).
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