Payne, on loan from Gillingham, was forced off shortly before half-time at the John Smith's Stadium on Saturday with suspected ankle ligament damage.
The 21-year-old midfielder is set for a scan but Posh boss Darren Ferguson already feels Payne may have made his last appearance for the club this season.
"It looks a bad one. We will organise a scan but we think he's damaged his ligaments and if that's the case he will struggle to play again this season," said Ferguson following the game in West Yorkshire.
Peterborough have endured some bad luck with loan players this season with Scott Wootton, Saido Berahino, Alex Pritchard and Davide Petrucci having all suffered long-term injuries during stays at London Road.
However, Tottenham midfielder Pritchard returned to the Posh squad at the weekend following two months out with an ankle problem.