Grimsby Town fell to their second consecutive single-goal defeat as managerless Leyton Orient won at Blundell Park.
The Mariners went behind on 20 minutes as substitute Dan Happe scored what proved to be the only goal of the game.
Orient hit the bar twice but could not add to their lead and Town had chances to snatch a share of the spoils, with Lenell John-Lewis hitting the post after coming off the bench in the second half.
But ultimately, they were unable to find the net and were left to reflect on a loss which left them at the bottom of League Two.
Boss Paul Hurst made four changes to his starting line-up following the 1-0 weekend defeat at Harrogate as he returned to the XI that began last week's home win against Crawley.
That meant Joe Bunney, Filipe Morais, Danny Rose and Joe Adams all returned, with Mattie Pollock, Luke Hendrie, Giles Coke and James Hanson making way.
Jake Eastwood started in goal, with Elliott Hewitt, Rollin Menayese, Luke Waterfall and Bunney forming the defence.
Morais, Rose, Jay Matete and Adams were the midfielders, with Idris El Mizouni supporting striker Stefan Payne.
Hendrie, Coke and Hanson were all named on the bench, along with James McKeown, Sam Habergham, Lenell John-Lewis and Julien Lamy.
Orient travelled north also looking to bounce back from a defeat after they lost at home to Tranmere, a result which led to the departure of head coach Ross Embleton and marked the club's seventh game without a win.
Interim manager Jobi McAnuff named two former Mariners in his first starting XI as Joe Widdowson lined up at left-back and midfielder Craig Clay wore the captain's armband.
An early Town free kick was cleared but Orient's Adam Thompson stayed down after a clash with Waterfall in the air. After a lengthy stoppage, he was unable to continue and the visitors were forced into making the game's first substitution as Happe came on.
Morais sent a weak effort wide of the target after a run through the middle on 12 minutes, before Hewitt was unfortunate to overrun the ball on the right as he looked to get a cross in.
The away side's first chance came on 15 minutes but James Brophy's shot was blocked and Town cleared.
A foul by Bunney gave Orient another opportunity to get the ball into the penalty area with a free kick on the right but Eastwood pushed the delivery from Dan Kemp away for a corner.
That signalled the start of a spell of Orient pressure which after a flurry of corners, eventually led to the opening goal on 20 minutes.
The Mariners survived when a first-time effort from Brophy on the edge of the box was deflected behind but after another corner was not fully cleared, a cross from Kemp fell for substitute HAPPE and he turned it past Eastwood and into the net.
Another Kemp free kick from the right was headed clear, before Matete shot wide at the other end as Town looked to respond to going behind.
But the visitors were looking the more dangerous of the two sides at the half-hour and they had another chance when Brophy cut in from the left, although he eventually fired over the bar.
A Hewitt long throw led to a Town corner but after the ball was initially played short, a cross from Morais was caught by Orient keeper Lawrence Vigouroux.
El Mizouni sent a 20-yard effort just over the bar after cutting in from the left on 35 minutes, before another Mariners corner came when the ball was cleared after a free kick had been played low to Payne in the box. Morais' ball from the flag fell for Waterfall but he could not get enough power on his header to trouble Vigouroux.
At the other end, a snap-shot from Danny Johnson produced a good save from Eastwood and Kemp could only send the rebound wide for a goal kick.
Payne looked to have a chance on 42 minutes after a ball by El Mizouni but Orient defender Jamie Turley got back well to beat the striker to it and clear for a corner, which was headed over the bar by Waterfall.
As the game moved into two minutes of added time, the away side were inches away from doubling their advantage as Brophy found Kemp inside the box but his first-time shot bounced back off the bar.
No further chances came before the referee's half-time whistle, leaving the Mariners with a one-goal deficit at the interval.
No further changes were made before the restart and the first opening of the second half went to the visitors but a shot from Nick Freeman was blocked and after the ball bounced around the penalty area, nobody could turn it towards goal.
A better chance came on 50 minutes as Orient hit the woodwork for the second time. The ball was worked to Kemp in space in the box and his shot beat Eastwood but came back off the bar.
Town had found attacking opportunities hard to come by in the second half so far but a run from El Mizouni led to an opening, although the midfielder's through-ball for Payne was just behind the striker and his weak shot was comfortable for Vigouroux.
Hanson and John-Lewis replaced Rose and Payne on 66 minutes as Town switched to a 4-4-2 formation in a bid to change the course of the game.
And the two combined three minutes later, with Hanson heading down for John-Lewis to fire a 20-yard drive which just missed the target.
Lamy was sent on in place of Adams in the hosts' third change on 72 minutes, with the Mariners now doing most of the attacking as they searched for an equaliser.
John-Lewis went close to levelling the scores after Hanson played the ball through for him but his low, first-time shot from the edge of the box hit the bottom of the post and was cleared for a corner.
Hector Kyprianou replaced Clay for Orient as Town continued to create chances, with John-Lewis heading at Vigouroux on 82 minutes.
Brophy hit a cross-shot wide of the far post from the left on 85 minutes, before Tristan Abrahams came on for Johnson in Orient's latest substitution.
A run by Brophy down the left led to an away corner on 88 minutes and another corner came on the right a minute later as the visitors aimed to run the clock down and hold on for all three points.
Two added minutes were played at the end of the game and Town were unable to force an equaliser as Orient closed the game out.
The Mariners are next in action on Saturday, when Forest Green Rovers are the visitors to Blundell Park.
44. Jake Eastwood
22. Elliott Hewitt
3. Joe Bunney
6. Luke Waterfall (C)
26. Rollin Menayese
4. Danny Rose
18. Filipe Morais
20. Jay Matete
45. Joe Adams
40. Stefan Payne
38. Idris El Mizouni
1. James McKeown
36. Sam Habergham
8. Giles Coke
9. James Hanson
21. Lenell John-Lewis
42. Julien Lamy
22. Lawrence Vigouroux
18. Tunji Akinola
3. Joe Widdowson
23. Jamie Turley
29. Adam Thompson
4. Ousseynou Cissé
8. Craig Clay (C)
28. Nick Freeman
39. Danny Johnson
15. Daniel Kemp
16. James Brophy
1. Sam Sargeant
5. Daniel Happe
2. Sam Ling
11. James Dayton
26. Hector Kyprianou
35. Tristan Abrahams
9. Conor Wilkinson
Referee: Stephen Martin
Next Up: Forest Green Rovers (H)