Castleford say they have just 14 fit first-team players after confirming three squad members have tested positive for coronavirus.
The Tigers confirmed the trio are self-isolating for a minimum of 10 days, in line with government guidelines.
A further six players have been stood down as part of the track and trace protocols ahead of Thursday's Super League game against Leeds at Headingley - live on Sky Sports.
With a number of injuries to contend with, Cas say they have just 14 players currently available but will check on the fitness of a further three on Thursday morning before a final decision is made on whether they can fulfil the fixture.
Castleford's first-team squad will be tested again on Friday morning.
"We've up to 20 players unavailable for various reasons, which is unprecedented across rugby league I think," head coach Daryl Powell said ahead of the Leeds game.
"It's really rattled us as a group. We're in a bit of trouble here, obviously with Covid and we've got a significant number of players who are injured.
"We've got 14 fit players and three who will be looked at in the morning who are real doubts. In a normal week, they wouldn't play. It's a really tough situation to be in.
"Obviously we want to play the game. We've had to do all sorts of things to keep our season going and have just got on with it.
"How this is going to pan out in the morning I just don't know. Clearly we can't go into a game with 14 players.
"It looks an impossible task at the moment, but we're leaving it as late as possible."
Powell's side have lost six of their last seven Super League matches, leaving them in eighth position going into the latest round of matches.