Midfielder Conor Grant left Home Park on crutches after Plymouth Argyle’s 5-0 Central League defeat by MK Dons on Tuesday afternoon.
The 23-year-old picked up an injury to his left leg in the second half of the game.
Grant crumpled in a heap on the ground after putting in a left-wing cross and it was soon evident he would be unable to continue playing.
He was helped to the Argyle changing rooms while Lionel Ainsworth was sent on as a 70th minute substitute for him.
It was only Grant’s third match since returning from a lengthy lay-off due to a calf injury.
His last first team appearance for the Pilgrims came in the 2-0 defeat by Sunderland at Home Park in November.
Now it appears the former Everton midfielder could have suffered a significant setback.
Argyle coach Kevin Nancekivell told Plymouth Live after the game: “The physios are with him at the minute and they will have a look.
“So fingers crossed it’s not too serious. We probably won’t know any more until tomorrow morning.
“I don’t think it’s his calf but I haven’t really had chance to speak to the physio yet, or Conor.
“We will see what happens tomorrow and I’m sure it will all come out then.”
Grant had made 14 starts and one substitute appearance for Argyle this season before his calf injury in November stalled his progress.
Nancekivell said: “Conor has missed a lot of football. He has just got himself back into it and started to look sharp and gain some match fitness.
“It (the injury) might not be too serious, we don’t know at the minute. We will try and look on the positive side and hopefully he will be fine.”
Another Argyle midfielder, Jamie Ness, continued his recovery from a calf injury by playing the whole Central League game against MK Dons.
Meanwhile, there has been no update from Argyle about the groin injury suffered by goalkeeper Kyle Letheren in the 2-0 League One defeat at Sunderland on Saturday.
Letheren had to be substituted in the second half at the Stadium of Light.
He was replaced for the closing stages of the game by Matt Macey, who started the Central League clash against MK Dons.
Macey conceded the penalty from which Robbie Simpson gave MK Dons the lead in the 24th minute.
Former Exeter City striker David Wheeler, who is currently on loan to MK Dons from Queens Park Rangers, went on to complete a hat-trick for them.