"As a result of the planned strike by the pilots' union Cockpit, around 3,800 flights will be cancelled on Wednesday, Thursday and Friday," the carrier said in a statement.
"A total 425,000 passengers will be affected by the stoppages," it said. "During the three-day walkout by Cockpit teams, there will only be around 500 short- and long-haul flights by Lufthansa and Germanwings."
Lufthansa said it would inform passengers via text message or email about the flight changes.
Most domestic and European flights on the strike days would be operated by Lufthansa Group companies Eurowings, Lufthansa CityLine and Air Dolomiti, whose pilots were not taking part in the strike, the statement said.
In addition to passenger services, the group's freight carrier, Lufthansa Cargo, will also be affected, with 23 out of 31 planned cargo flights from Frankfurt being cancelled.
The union, Cockpit, called for three full days of strikes last week, just a day after Lufthansa was forced to cancel around 600 flights following stoppages by ground staff, baggage handlers and maintenance workers at Germany's main airports.
In a strike ballot earlier this month, pilots from Lufthansa, Lufthansa Cargo and Germanwings voted 99.1 percent in favour of possible strike action in pursuit of their demands for higher pay and better provisions for pilots nearing retirement age.