The bus where the French tourists were travelling hit another vehicle in the nothern region of Varadero in Cuba.
Most of the 41 were retired people from the city of Ouistreham in Normandy.
The Cuban driver and the tour guide were also hurt and all the 43 injured were taken to hospital in Cienfuegos, 250 kilometers away from Havana.
French Prime minister Manuel Valls said in a statement " everything was organised for an emergency repatriation in France".
The accident came following a visit to a monument to Che Guevara said the French Embassy in Cuba.
It's the busiest season for Cuban tourism a time when thousands of visitors from Europe, Canada and Latin America flock to the Island.