The strike has seen at least 32 flights between France and Spain struck from departure boards, Spain's airports authority AENA reported on Tuesday.
Half of all flights to Paris, Lyon, Nice, Marseille, Toulouse and Bordeaux have been cancelled, the country's DGAC civil aviation authority said.
France's traffic controllers downed tools at 6am on Tuesday on what is the first of three planned days of strike action.
The country's traffic controllers are complaining about work conditions and the liberalization of air space resulting from the European Union's Single European Sky initiative, Spain's Te Interesa news site reported on Tuesday.
Europe's air safety body Eurocontrol has warned of possible delays and problems with all flights through French air space.
AENA is recommending that passengers check with airlines before travelling.