The Scotland internationalist was forced off midway through the first half of the Easter Road side’s goalless draw with Celtic last weekend and left the stadium on crutches and wearing a leg brace,.
“We know his season is done and we have to prepare for it being longer than that,” Maloney said.
Asked if it might be an ACL injury, Maloney added: “It doesn’t look good. It is definitely season-ending, but it could be a lot longer than that.
"It’s going to be a really big hurdle to overcome and if the injury is what we think, then other players have had similar injuries and come back even better players.
"Kevin’s mindset has to be that, whatever hurdle this is, whatever length of time it takes, he comes back a better player.”
As things stand Maloney will be without at least ten players for the visit of St Johnstone on Saturday.
Defender Rocky Bushiri is suspended for the match with Callum Davidson’s side and the Scottish Cup trip to Motherwell next weekend after his red card against Dundee, while Chris Mueller is ill and won’t feature against the Perthshire side either.
As well as Nisbet, long-term absentees Harry Clarke, Paul Hanlon, Kyle Magennis, Paul McGinn, Demi Mitchell, and Joe Newell remain sidelined. There is a chance James Scott could make the squad but Matt Macey will again miss out.
"James might make it. He has put himself forward after a chest infection but we will see – at the moment we still have 11 players out, which is quite difficult,” Maloney continued.
“It’s a quad and groin injury Matt sustained. We’ll see how he goes next week.”
Macey’s absence means Kevin Dabrowski will continue in goals but Maloney may need to call on the experience of Darren McGregor in defence.
“I’ve leaned on him very heavily as a senior player, in terms of the culture we’re trying to create,” Maloney said.
"Darren’s been a brilliant professional since I’ve been here, so I can’t speak highly enough of him and I’m sure if selected he’ll be absolutely fine to go.”