Wayne Rooney and Derby's first-team squad will miss Saturday's third-round FA Cup tie at Chorley following the coronavirus outbreak which closed their training ground on Monday.
The Rams team for the game at Victory Park will be made up of under-23 and under-18 players.
Under-23 coaches Pat Lyons and Gary Bowyer are likely to take charge.
The Moor Farm training facilities were closed after a number of players and staff tested positive for Covid-19.
On Monday the club said they were "in dialogue with the EFL and Football Association in relation to upcoming fixtures".
In a further statement issued on Wednesday, Derby said: "The club have been in dialogue with the Football Association since Monday evening to discuss potential ways forward for this weekend's FA Cup tie.
"Those that have tested positive for Covid-19, and those that have been in close contact with those individuals, must self-isolate for a period of time.
"As the first-team coaching staff, backroom team and players are currently self-isolating, staff and players at Saturday's match will be predominantly made up from the club's under-23 and under-18 set-ups.
"All individuals scheduled to attend the fixture at Chorley, in line with Football Association rules, will be tested for Covid-19 on Thursday."
FA Cup rules state that clubs are expected to fulfil their fixtures if they have 14 eligible players - including from the under-23 and under-18 squads - available, although there is scope for appeal.
Former England striker Rooney has been in interim charge of Derby since previous manager Phillip Cocu's exit on 14 November.
The Rams are third from bottom in the Championship having played 22 matches.
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