Mainz, who have around a dozen players in COVID-19 quarantine, struck early to stun last season's Bundesliga runners-up RB Leipzig 1-0 on Sunday and spoil new coach Jesse Marsch's first league match in charge.
The game had been in doubt after several Mainz players and coaching staff tested positive for COVID-19 and 11 players and three staff were sent into isolation.
Mainz's Moussa Niakhate tapped in at the far post in the 13th minute, however, after a disastrous Leipzig attempt to clear the ball sent it into his path.
In a largely one-sided second half, Leipzig pushed Mainz back deep but struggled to create openings, although they did come close with Mohamed Simakan's double chance on the hour and Mukiele's shot.
"It wasn't how we were hoping to start the season," Leipzig coach Marsch, who succeeded Julian Nagelsmann, said.
"Mainz sat back and defended after their goal and fought for every ball. That didn't leave much space for us. It definitely wasn't our best game, but we will continue to work.
"In total not our best day. It is okay that when we have the first tough result we are still a work in progress," American Marsch added.