"The president announces with deep sadness the death of 13 French troops in Mali on the evening of November 25, in an accident between their two helicopters during a combat mission against jihadists", an official Elysée statement said.
The US has said West Africa's Sahel region is an emerging front in the fight against Daesh and other militant groups, including those linked to al Qaeda.
While the initial operation to free northern Malian towns from extremists took only a few months, the threat has since metastasised, spreading to southern Mali as well as neighbouring Burkina Faso and Niger.
Shortly after troops engaged the insurgents fleeing on motorbikes and in a pick-up truck, a Tiger attack helicopter collided with a Cougar military transport helicopter.
Since August 2014, France's anti-insurgent Operation Barkhane has had around 4,500 troops deployed in five West African countries: Burkina Faso, Mali, Mauritania, Niger, and Chad.
"Europe is not immune to these security concerns", said Armed Forces Minister Florence Parly.
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The 13 troops were killed during a counterterrorism combat operation in Mali, when the two helicopters the troops were on slammed into each other. It was the heaviest loss for the French army since the 1983 attack on the Drakkar building in Beirut, claiming the lives of 58 paratroopers.
Forty-one French soldiers have been killed in Mali since France launched its Barkhane counterinsurgency operation against Islamist militants in the Sahel in 2014.
France's operation became involved in the Liptako area in 2017 and this year it built a new base in Gossi in the Gourma region, IISS said.
Britain and the U.S. also have a military presence in the area, but Paris has failed to convince European Union allies to contribute significant troops to the Sahel fight.
Since January, more than 1,500 civilians have been killed in Burkina Faso and Mali, and more than one million people have been internally displaced across the five countries - more than twice the number of persons displaced in 2018, the United Nations said this month.
The territory was recaptured by Mali's army with the help of France but insecurity still persists in Mali.
President Macron said in a Tweet on Tuesday: 'Thirteen of our soldiers died yesterday in Mali.