Having experienced extra-time heartbreak in the FA Youth Cup in midweek, the young Greens fell to disappointing defeat against Oxford United at Bolitho Park.
The Pilgrims dominated periods of what turned out to be a very frustrating game at the home of Plymouth Parkway, with an own-goal and a missed penalty contributing to the end result.
Argyle coach Jamie Lowry said: "This was not a case of Oxford being better than us, as we competed well in the game, but you cannot give sides silly goals like we did.
"The own goal, the penalty and giving their player the freedom of the area for the third, and then we miss a penalty as well and that was the main difference between the two sides.
"They are only young, and this is all about them learning and developing, and that is what we are here to help them do.
"We have to make sure that they bounce back bigger and stronger from games like this, which is all part of their learning curve.”
Argyle had the first chance to score when the impressive Will Jenkins-Davies found Oscar Halls wide on the right, but Scott Crocker's header was well saved by Eddie Brearsy.
The young Pilgrims were enjoying the majority of the play and looked well placed to capitalise, before gifting the visitors a 27th minute lead, as central defender Ethan Mitchell unfortunately turned Tyler Goodham's corner into his own net.
This was the boost that Oxford needed, and goalkeeper Tyler Coombes had to make a fine save to keep out Clinton Nosakhare's blistering drive.
Matters were complicated on 43 minutes, when Jenkins-Davies’ mistimed challenged on Goodham presented the visitors with a penalty – which Callum Crook converted.
Argyle battled hard after the break, and earned a great chance to pull a goal back - but Scott Crocker's penalty was saved by Brearsy, who recovered well to beat out the Argyle striker's follow-up effort.
The Greens were made to pay for that miss as, eight minutes later, it was 3-0 – with substitute Gatlin O'Donkor sweeping his shot across Coombes and inside the far post.
Coombes had made another fine save, from Will Owens' near post header, before Argyle gained a late consolation in the third minute of stoppage time.
Substitutes Rhys Shirley and Carlo Garside combined for the latter to lash the ball into the bottom corner from 12 yards.
Plymouth Argyle: Tyler Coombes, Oscar Rutherford (Charlie Miller half-time), Brandon Pursall (Jeremiah Medine 62), Finley Craske, Ethan Mitchell, Oscar Halls, Will Jenkins-Davies, Scott Crocker, Jamal Salawu (Carlo Garside 85), Angel Waruih, Oscar Massey (Rhys Shirley half-time). Substitutes not used: Lewis Moyle, Ali Mansaray.