Air France's regional subsidiary, CityJet, will cease flying between Shannon, Ireland, and Paris Charles de Gaulle from 24 October.
The airline blames the economic downturn for a "steep decline" in traffic on the route, which was performing well as recently as early 2009.
CityJet began its Shannon-Paris service in February 2008, aiming the link at business travellers.
However, recession has stifled demand and the airline "cannot foresee passenger numbers and revenues reaching a break-even level".
CityJet plans no further route closures for the winter, while Air France-KLM says it remains "strongly committed" to the Irish market.