Carlisle United 0 Nottingham Forest U21 2: Carlisle produced an underwhelming display to lose to Forest's B Team in the EFL Trophy at Brunton Park.
In front of just 1,268 fans, a much-changed United XI failed to produce any inspiration as they were left on the brink of group-stage elimination.
Josh Powell and Ben Perry struck in the second half for the Premier League visitors with United unable to reply.
Ryan Edmondson and Owen Moxon struck the woodwork but it was a second successive defeat for the Blues in the competition.
They must now win their last game against Harrogate Town, hope Forest U21s lose to Accrington Stanley and also benefit from a goal difference swing to reach the knockout stages.
Simpson made ten changes to Saturday's side with Ben Barclay making his first appearance for two months in defence.
Callum Guy was the only of Saturday's XI to be retained in the team, with Jokull Andresson, Jack Ellis, Jack Robinson, Corey Whelan, Jayden Harris, Dan Butterworth, Edmondson, Terry Ablade and Luke Plange also called up.
Forest, though, began the brighter with frontman Ateef Konate a regular threat.
The young visitors were quicker and sharper in the opening stages despite the seventh-minute loss of Pharell Johnson to injury.
Konate twice went close and it took Carlisle until the half-hour mark to have a sustained spell, a flurry of corners almost producing an opener.
But Barclay couldn't get enough on Butterworth's delivery, and then Edmondson hit the outside of the post from Robinson's corner.
Harris shot over following another set-piece but Konate remained a threat, testing Andresson late in the half before Barclay shot wide for Carlisle from distance.
Simpson brought on Moxon for Guy at the break and United began the second half on the front foot, Moxon, Ablade and Butterworth having shots blocked.
Barclay was then withdrawn after 62 minutes of his comeback outing, Jon Mellish stepping up from the bench.
Yet it was Forest's Under-21s who then took control of things after Konate had again gone close, and in the 69th minute Powell opened the scoring when his shot from the left took a slight deflection and beat Andresson at his near post.
Butterworth was denied a quick leveller when his powerful shot was saved by keeper George Shelvey, and then the visiting keeper pushed a Moxon free-kick against the post.
Simpson made a triple change to try and get back into the tie, Sean Maguire, Jordan Gibson and Alfie McCalmont coming on.
But the visitors then doubled their lead 13 minutes from time, Ben Perry finishing past Andresson after some skilful work in the box.
The visitors then saw captain Sam Collins suffer a serious looking injury as he was eventually stretchered off in the closing stages after a challenge with Moxon.
Carlisle could not find a way back in eight added minutes in front of Brunton Park's 17th-lowest crowd of all time, and an early exit from the competition now looks likely.
United: Andresson, Ellis, Robinson, Barclay (Mellish 62), Whelan, Guy (Moxon 46), Harris (McCalmont 76), Butterworth, Ablade (Maguire 76), Edmondson (Gibson 76), Plange. Not used: Breeze, Armer.
Booked: Robinson, Butterworth, Plange.
Nottm Forest U21: Shelvey, Konate, Gardner, Powell, Johnson (McAdam 7), Perry (Sinclair 83), Collins (Norkett 90), Hammond, Hanks, Thompson, Perkins. Not used: Bott, Clarridge, Larsson, Whitehall.
Goals: Powell 69, Perry 78.
Booked: McAdam.
Ref: Thomas Kirk.
Crowd: 1,268 (106 Nottm Forest U21 fans).
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