Dynamo Dresden, who play in the second tier of German football, have put their entire squad and coaching staff into two-week isolation after two players tested positive for coronavirus.
The Bundesliga and Bundesliga 2 are due to restart on Saturday, 16 May.
It is set to be the first European league to restart following the coronavirus shutdown.
"The fact is that we can neither train nor participate in a game in the next 14 days," said Dynamo.
On Thursday, the German Football Association (DFB) said the season would resume under strict health protocols that ban fans from the stadium and require players to have Covid-19 testing.
About 300 people, including players, staff and officials, will be in or around the stadiums during match days.
The league has been suspended since 13 March. Clubs returned to training in mid-April, with players working in groups.
But on Saturday Dresden, who are bottom of Bundesliga 2, said they would be unable to fulfil the initial fixtures.
"In the past few weeks, we have made enormous efforts in terms of personnel and logistics in order to strictly implement all the prescribed medical and hygienic measures, "said Dynamo sports manager Ralf Minge .
"We are in contact with the responsible health authority and the DFL (German Football League) to coordinate all further steps."
Dresden were due to resume the season on 17 May at Hannover 96.
John Bennett, BBC World Service
The Dynamo Dresden situation proves that any league will be balanced on a knife edge when football resumes, even with all the planning and all the expertise that has gone into the Bundesliga restart.
DFL boss Christian Seifert admitted as much on Friday when he said that they are "playing under probation".
The truth for football authorities everywhere is that there are no certainties at the moment and there will be setbacks.
The only good news is that although there are a lot of fixtures to pack in, time is relatively on German football's side compared to the other big European leagues, who are still wondering if and when they'll be able to return.
Now the DFL will be hoping that this will be the only fixture they'll have to postpone on their high profile re-opening weekend.