The typical changing conditions in Le Mans left the premier class in a confusing situation, as they started the final practice session on slick rubber fit for a drying track but clouds changed their mind and started shedding more water so the woolly hats went back on while riders waited for Le Mans to make up its mind. The track finally got busy for the final 15 minutes of the session, when Fabio Quartararo went fastest on a drying track, but only seven thousandths of a second ahead of Alex Rins. Franco Morbidelli finished third despite slightly twisting his ankle in a practice bike swap at the end of FP3.
The Repsol Honda duo of Pol Espargaro and Marc Marquez completed the top five, although both riders took a tumble within seconds of each other in the final handful of minutes, as rain started falling once more. Miguel Oliveira and Joan Mir were also within two tenths of a second of the leader, with Takaaki Nakgami, teammate Alex Marquez and Iker Lecuona rounding out the top ten. Maverick Viñales in 11th position was six tenths off top spot, while Johann Zarco and Jack Miller did the most running but were only 16th and 17th in the end.