Manuel Neuer and Thomas Muller – pillars of the Germany national team over the last decade – are battling to prove their fitness with barely three weeks remaining until the World Cup begins.
Bayern Munich boss Julian Nagelsmann confirmed in a press conference on Friday that neither player will be fit enough to feature in Saturday's Bundesliga game against Mainz.
Goalkeeper Neuer remains troubled by a shoulder issue, while attacking midfielder Muller has a hip problem, and Nagelsmann could not say with conviction when both will be back in club action.
The news will inevitably be a worry for Germany boss Hansi Flick, as the former Bayern head coach finalises his plans for the Qatar 2022 finals.
Muller played for half an hour as a substitute in Bayern's 3-0 win at Barcelona on Wednesday, but the 33-year-old will not be risked at all against Mainz, and almost certainly will also sit out the Champions League meeting with Inter next Tuesday.
"He has irritation in his hip again, in the pelvic area," Nagelsmann said. "He won't be able to play, probably not even on Tuesday. We'll probably have to take him out for a week to give him a break.
"Thomas is in good spirits. We talked to a couple of medical professionals yesterday and tried to get a better picture of everything, but the picture didn't really change.
"It's not something that goes away with pain medication either. It feels blocked, and it's difficult to define how the pain is manifesting itself. I decided it would be better just to take him out of action for the time being.
"[Saturday] is the type of game where even for 10 or 15 minutes you have to give absolutely everything, so if we give him that 10 or 15 minutes, he's ultimately going to have to drop out potentially for the next game. We've got to see how it develops and how it reacts.
"The key right now is instead of blindly testing it out constantly, to give it a bit of calm and see how it reacts to that and then see how his recovery goes."
Neuer, the 36-year-old captain of Bayern and Germany, has played no active part since Bayern's 2-2 draw at Borussia Dortmund on October 8.
It is obvious to Nagelsmann that having Neuer fit is not only a priority for Bayern but a matter of national interest.
There are no promises at the moment, but Nagelsmann is hoping Neuer may be able to return next weekend at Hertha Berlin.
"I'm not a mystic that can see into the future," Nagelsmann said. "We put him in the game against Dortmund and maybe that was a game too early, and now he's sat out a couple of games.
"It's very difficult for me to know how the pain will be managed. It's a structural area of the body that needs time to heal and a joint that needs a bit of calm as well, so if you're constantly testing it and putting a burden on it, it can be tough.
"I'm anticipating he will be ready for the World Cup, but I'm not a psychic. We're going to do everything we can to help him be there for the World Cup."
Bayern are the hosts on Saturday against a Mainz team who led at the Allianz Arena last season before slipping to a 2-1 defeat.
However, Mainz have beaten Bayern twice in the past two seasons, both times when having home advantage.
Among sides currently in the top flight, only Augsburg have also taken six points from their last three matches against Bayern – no teams have managed more.
Heading into this meeting, Bayern and Mainz have both won their last two games, each scoring seven goals and conceding none – a league high in this timeframe.
Mainz are also top of the away form table this season with 12 points from six away games, marking them down as a threat.
Bayern nevertheless head into the weekend programme just one point behind early leaders Union Berlin, who must wait until Sunday before tackling Borussia Monchengladbach.
"We're in a good rhythm right now," said Nagelsmann. "Against Barcelona, we looked like a solid unit who all had the same goal in mind. The team have a great connection with one another."