The Spremberg mine is in the Lausitz basin -- where thousands of jobs depend on coal but where residents are also opposed to a planned expansion of mining.
The mine produces 22 million tonnes a year of lignite, a low-grade type of brown coal that is also considered the most harmful to human health and the environment.
"Despite all the nice speeches and promises, 2019 was another lost year for the climate," said Nike Malhaus, spokeswoman for the anti-coal group Ende Gelaende (Game Over) which is organising the protest action.
The occupation is being supported by other environmental groups, including the German branch of Fridays for Future which is organising its own protest on Saturday in front of a nearby power station.
It will be the second time this year that Ende Gelaende has occupied a coal mine. In June, several hundred climate activists carrying sleeping bags blocked the vast Garzweiler lignite mine near Cologne for several days.
Campaigners say the government's plans to phase out coal by 2038 announced this year do not go far enough.
They want that date brought forward for Germany to meet its international commitments to slash carbon pollution.
"The plan is totally empty. It's a scandal, a crime against future generations," Malhaus said this week.
- Far-right surge -
The mining industry in the Lausitz, which stretches all the way into Poland, is vital to the local economy.
Czech-controlled LEAG, which owns Spremberg, is one of the region's largest employers with 8,000 workers.
Opposition to the government's plants to shut down coal mines was seen as a factor behind a surge for the far-right AfD party in regional elections in September.
The AfD is now second after the centre-left Social Democrats in Brandenburg region where Spremberg is located.
The party was planning a protest on Friday against the occupation, raising concern about possible clashes.
The local council in Cottbus, a city a few kilometres from the Lausitz basin, passed a motion condemning the occupation with the support of all parties except the Greens.
Malhaus admitted there was "a climate of defiance towards our movement on the local level".
But she also pointed to local support in the Lausitz.
"We have a lot of campaigners here so it's not true to say that all inhabitants of this region are in favour of coal," she said.
LEAG has also faced strong opposition to its plans to expand lignite mining in the region, which would result in the resettlement of two villages.
Germany's decision in 2011 to abandon nuclear power following the Fukushima disaster in Japan has made the country more dependent on coal as renewables struggle to fill the gap.