LATAM Airlines Group will end service between Sao Paulo Guarulhos and Rosario from 1 July.
"The decision was based on the effect of the devaluation of the Argentine peso and demand," says a LATAM spokesperson.
The Oneworld carrier is the only airline operating nonstop between the two cities, Cirium schedules data show.
LATAM has trimmed its network in recent months in response to macroeconomic conditions in Argentina. It previously confirmed it will end service between Brasilia and Buenos Aires from 2 May.