Tranmere were unable to repeat their FA Cup win over Leyton Orient as they fell to a 2-1 defeat at the Matchroom Stadium in Coca-Cola League One.
Rovers went behind midway through the first half but levelled soon after through Charlie Barnett's first goal of the season.
However, Orient netted once more after half time and Tranmere couldn't find a way through to goal a second time.
There was just one change to the side that had defeated Orient five days earlier, with John Welsh returning from suspension to take the place of Shaleum Logan. Welsh took the place of Ash Taylor in midfield who dropped back into the centre of defence with Marlon Broomes switching to right back.
Orient's Ryan Jarvis had the game's first shot on 11 minutes but his effort on the turn went wide of Luke Daniels' goal. A minute later Craig Curran's long range effort was comfortably held by Glenn Morris at the opposite end.
The sides continued to trade possession with Scott McGleish missing from 12 yards on 16 minutes while Zoumana Bakayogo shot wide for Rovers soon after.
McGleish gave Orient the lead with his next effort on 23 minutes when, after breaking free of the Tranmere back line he sent a low shot past Daniels into the net.
Rovers looked for an immediate response, with Ian Goodison heading straight at Morris from a corner two minutes later.
A Luke Summerfield free kick deflected off the wall for a corner on 27 minutes, while Goodison had to be replaced by Aaron Cresswell a minute later due to injury.
Cresswell had barely been on the pitch a minute when Rovers levelled. Welsh's long range effort wasn't held by Morris allowing Barnett to close down and&nbsp;turn in the rebound.
Former Rovers defender Ben Chorley cleared a Chris Shuker free kick out of the path of Taylor on 33 minutes and Welsh sent another effort narrowly over the bar with his left foot five minutes later.
Tamika Mkandawire headed over the Tranmere goal from close range on 41 minutes and McLaren volleyed over in injury time at the other end. Jarvis broke free for Orient&nbsp;moments later and went one on one with Daniels, but Bakayogo was quickly back to clear the danger.
A cross from Andros Townsend went straight through the Rovers area on 56 minutes while Morris caught another effort from distance from Welsh as both sides looked for the lead.
It was Orient who went back ahead on 70 minutes, with McGleish netting his second of the afternoon when he got in front of his marker to head in Sean Thornton's corner.
Kithson Bain was brought on in place of Curran with 16 minutes remaining and ten minutes later Michael Ricketts replaced Ian Thomas-Moore.
However, the pair were unable to make a significant impact on the game as Rovers failed to find the equaliser.
Leyton Orient: Morris, Purches, Chorley, Mkandawire, McGleish, Thornton, Daniels, Jarvis (Patulea 62), Summerfield, Smith, Townsend. Substitutes not used: Jones, Ashworth, Chambers, Demetriou, Cave-Brown, Scowcroft.
Tranmere: Daniels, Broomes, Taylor, Goodison (Cresswell 28), Bakayogo, Welsh, McLaren, Barnett, Shuker, Thomas-Moore (Ricketts 84), Curran (Bain 74). Substitutes not used: Collister, Baker, Fraughan, Gornell.
Referee: Darren Sheldrake
Yellow cards: Curran (42), Charlie Daniels (45), Taylor (65)