Tranmere were beaten 1-0 by Northampton Town at Sixfields as a second half Ryan Cresswell header was the difference between the two sides.
Manager Micky Adams made four changes to the starting line-up from last weekend with Michael Ihiekwe, Liam Ridehalgh, Dan Gardner and Kayode Odejayi coming in to replace Adam Dugdale, Rory Donnelly, Jason Koumas and Jordan Hugill.
The home side named former Rovers left-back Evan Horwood in their starting XI against his former club.
In the opening five minutes, Owain Fon Williams was called into action to make a good save to deny Northampton forward James Gray before making a similar stop from a Ricky Holmes effort.
At the other end, Josh Thompson headed a Max Power corner wide with Tranmere's first effort of the afternoon.
On 20 minutes, Brendon Moloney found himself on the right side of the penalty area but his effort was blocked by Janoi Donacien before Fon Williams claimed the ball.
Two minutes later, Holmes cut inside off the right flank and hit a powerful shot which Fon Williams tipped over the crossbar.
Rob Taylor tried his luck from distance on 27 minutes but the effort was straight at the goalkeeper.
On 38 minutes, Northampton hit the woodwork as Lawson D'Ath cut inside from the left and hit a curling effort which clipped the top of the crossbar and drifted out for a goal kick.
Fon Williams made another save a couple of minutes as he held onto a vicious 25 yard volley from John-Joe O'Toole.
Tranmere had a shout for a penalty moments later as Jennison Myrie-Williams went down in the area but the referee waved play on.
At the other end, Holmes had a shot blocked by Fon Williams before Taylor limped off and had to be replaced by Rory Donnelly on the stroke of half time as the sides went in at the break with the scores goalless.
Rovers had the opening opportunity of the second half as Power played Dan Gardner in down the left but his cross evaded a touch as it fizzed across the face of the goal.
On 55 minutes, Gray fired in a shot from the right edge of the penalty area which Fon Williams tipped around the near post while three minutes later, a corner from the right was headed wide of the target by Gray.
Rory Donnelly tested Northampton goalkeeper Matt Duke moments later with a shot which was only parried before cleared to safety by The Cobblers' defence.
Northampton took the lead after 62 minutes. A free-kick from the left was swung in by Darren Carter and headed home by Ryan Cresswell past Fon Williams at the far post.
Donacien blocked a shot by D'Ath on 70 minutes before Tranmere made their second change with Jordan Hugill replacing Josh Thompson.
Cresswell was close to adding a second on 74 minutes but his header from Carter's right wing corner went wide.
Gray dragged a shot wide of the post on 77 minutes before Rovers made their final change of the afternoon with Steve Jennings being replaced by Chris Shuker.
Donnelly had a strike from 25 yards with four minutes remaining but his attempt flew over the crossbar.
A minute later, Tranmere struck the woodwork as Power's corner from the right was met by the head of Kayode Odejayi whose effort was tipped onto the crossbar acrobatically by Duke.
In the third minute of second half additional time, a left wing cross was headed wide by Michael Ihiekwe but Northampton held on to their advantage.
Yellow cards: Carter (60), Myrie-Williams (60), Ihiekwe (61).
Attendance: 4428 (281 away).
Northampton: Duke, Moloney, Cresswell, Collins, Horwood, Taylor, Carter, D’Ath, O’Toole (Toney 82), Gray (Newey 83), Holmes (Hackett 69).
Substitutes not used: Jalal, Bodin, Perry, Diamond.
Tranmere: Fon Williams, Donacien, Ihiekwe, Thompson (Hugill 71), Ridehalgh, Myrie-Williams, Power, Jennings (Shuker 78), Taylor (Donnelly 45), Gardner, Odejayi.
Substitutes not used: Ramsbottom, Holmes, Dugdale, Laird.