Rovers fell to a 4-0 defeat at home to League 1 leaders Leyton Orient on an eventful Saturday afternoon.
Kevin Lisbie's brace either side of half time put the visitors in control before Tranmere were reduced to ten men following the sending off of Ian Goodison.
Strikes from Dean Cox and Shaun Batt added to the scoreline late on with the loss keeping Rovers in the bottom four.
Ronnie Moore named an unchanged starting eleven from the win at Bradford City though Jason Koumas returned from injury to take the place of Callum Morris on the substitutes' bench.
Liam Ridehalgh's early header was comfortably held by Orient keeper Jamie Jones while on seven minutes the visitors had an excellent chance to open the scoring. A series of passes around the edge of the Tranmere area led to Moses Odubajo running on to a through ball only to fire wide when one on one with Owain Fon Williams.
Ryan Lowe's attempt on goal from a Chris Atkinson corner on 18 minutes was miss hit, while Max Power sent a left foot effort wide of the target from 20 yards soon after.
However, the visitors took the lead on 22 minutes. A long run from Lloyd James saw the midfielder get into the left side of the Rovers area and his low cross was turned in by Kevin Lisbie from near the penalty spot.
Rovers were close to an equaliser four minutes later. A free kick was whipped towards the back post by Atkinson and Ash Taylor's downward header was turned on to the post and away from goal by Jamie Jones.
Jake Kirby's first time shot from a half cleared Ridehalgh cross was blocked by the Orient defence on 34 minutes and the young midfielder had another chance five minutes later. Running on to a ball over the defence from Lowe, Kirby held off Odubajo and side stepped the defender but he lost control of the ball and Jones gathered.
Two minutes later Orient almost doubled their advantage, but Mathieu Baudry's close range header from Nathan Clarke's cross hit Fon Williams' bar and bounced away before being cleared by Taylor.
As the game went into added time at the end of the first half Lowe and Atkinson closed down Baudry with the latter appearing to get possession of the ball before going to ground as he ran into the area, however appeals from the home fans for a penalty were ignored by the referee.
Orient again went close on 47 minutes. Odubajo got past Goodison and into the area and his cross was turned back across goal by Dean Cox and David Mooney couldn't make contact to turn in a couple of yards from goal.
A Chris Atkinson shot deflected off a defender straight to Jones on 51 minutes and nine minutes later Orient went 2-0 up. A shot from Cox was heading out for a goal kick but Lisbie diverted it straight past Fon Williams into the top right corner.
After Rovers replaced Ridehalgh and Tom Hateley with Abdulai Baggie and Akpo Sodje, they were soon reduced to ten men. After clearing a cross into the Tranmere area, Goodison tangled with Lisbie and was shown a straight red card. After a couple of minutes of protests it became clear a penalty had been awarded to Orient. Mooney's spot kick hit the left hand post but rebounded straight to the striker who turned it into the net for what appeared to be his side's third goal. However, as the Orient players celebrated the referee spoke to one of his assistants before ruling out the effort and awarding Tranmere a free kick.
Orient did get their third on 77 minutes. The ball fell to Cox on the edge of the area and his right foot shot found the bottom right corner.
And the fourth followed on 85 minutes. After a cross from Power had been cleared Orient quickly broke, the ball was played to substitute Shaun Batt and he fired across Fon Williams and into the bottom right corner from a tight angle.
Tranmere: Fon Williams, Holmes, Taylor, Goodison, McNulty, Kirby, Power, Hateley (Sodje 62), Atkinson, Ridehalgh (Baggie 62), Lowe. Substitutes: Watkins, Horwood, Rowe, Koumas, Stockton.
Leyton Orient: Jones, Omozusi, Vincelot, Cuthbert, Baudry, Cox, James, Lisbie (Batt 72), Mooney (Stockley 85), Odubajo (Lasimant 81), Clarke. Substitutes: Sawyer, Larkins, Gorman, Bartley.
Referee: Richard Clark
Yellow cards: Ridehalgh (45+1), Baudry (55), Lowe (78)
Red card: Goodison (63)