The country's national weather service Météo France raised the alert level from orange to red for the southern departments of Herault, Gard, Vaucluse and Bouches-du-Rhone.
The move marks the first time since the warning system was brought in in 2004 that parts of the country have been on red alert for the a heatwave, called a canicule in French.
The warning level has been raised because temperatures in the south are forecast to reach as high as 44C on Friday.
The mercury is set to rise to 42C in Montpellier on Friday and touch 43C in Arles and Avignon.
Some 74 other departments around France, basically most of the rest of the country apart from Brittany and the far north, remain on Orange alert.
The red level alert, which is for a “dangerous weather phenomenon” comes with some warnings for the public to take the upmost precaution.
Météo France said “all of us are threatened, even healthy people”.
Also on Friday the country's rail provider SNCF announced it would allow passengers to cancel train tickets booked over the coming days free of charge, due to the heat.
The cancellations must be done in advance and apply to all train travel.