An unspecified group of unknown players have been showing some symptoms and the Terriers are now waiting on tests, the results of which they hope to have on Thursday evening.
It shows the precarious position clubs are in during the pandemic, and why coach Carlos Corberan was keen to have a deeper squad this season.
"Some of the players who played in the previous game (at Sheffield Wednesday in the League Cup) have shown some symptoms and went through some tests which created some doubts," said Corberan.
"We are waiting for the results this evening and we hope we won't lose any players to this situation.
"By the end of the day we hope to have some results.
"I can't give any confirmation (of numbers or identity) because we don't have any confirmation yet. Depending on the results we will prepare for the game on Friday.
"It's a challenge for everyone but unfortunately we need the habit to live with it because it's clear until everyone has the second vaccine the situation won't be under control.
"Our players are young players and the young people are the last people to get the vaccine. All the processes are under control, all the teams are going to be managing the situation."
Like many clubs this summer, Huddersfield have been affected by Covid cases, with Fraizer Campbell, Danny Grant and Rarmani Edmonds-Green, since loaned to Rotherham United, all suffering from the virus. All are now recovered, albeit Grant's progress has been slower, and is likely to keep him out of Saturday's game.
Although the Football League only requires its clubs to test players when they show symptoms this season, the Terriers have chosen to do so twice a week, with anyone showing symptoms sent for further tests.
Huddersfield treated the game against the Owls with the respect it merited as a competitive game, and the team selected can therefore be assumed to be what the Spanish coach considers his best. The Terriers won the game 4-2 on penalties after a 0-0 draw.
Saturday's hosts Derby have huge problems themselves, left with a threadbare squad by financial problems and a transfer embargo.