Rennes midfielder M'Vila took a kick to the ankle from Dusan Tadic in the opening exchanges and although he tried to carry on he left the pitch in obvious distress with just four minutes on the clock.
His team-mates went on to win with ease, scoring early goals through Franck Ribery and Florent Malouda while creating several other chances, but it will be the diagnosis for his central lynchpin that will most concern Laurent Blanc on Thursday night, with less than two weeks until the start of their Euro 2012 campaign.
He would later return to the bench without crutches, but a scan is still expected on the ankle with a clear concern as to his fitness.
France were still rocking from the loss of M'Vila when Ribery lifted the mood at the Stade Auguste-Delaune in Reims, rifling in a loose ball in the 10th minute after Zeljko Brkic spilled Gael Clichy's cross.
Moments later, Malouda's first-time pass had Karim Benzema through one-on-one with Brkic and the goalkeeper did well to palm it away for a corner.
Malouda then doubled the lead in the 16th minute with a stunning strike, taking advantage of sloppy play from Serbia on the edge of their area to power home a swerving shot that was never going to be stopped by the fingertips Brkic got to it.
France were buzzing now, and Ribery and Benzema linked up well on the right, with Ribery almost feeding the Real Madrid man for an easy finish only to see him lose his footing at the vital moment.
Yohan Cabaye's deflected shot then went narrowly wide while Benzema's cute flick from Ribery's cross was blocked by a despairing hand from Brkic.
Serbia's first chance of the match came in the 43rd minute when Bosko Jankovic screwed a free-kick wide, but it was a taste of things to come as the visitors looked much improved in the second half as the substitutions began.
Branislav Ivanovic flashed a shot narrowly wide soon after the break, but there was a scare for the Serbs moments later when Brkic fluffed a backpass and was lucky to see the ball roll wide of the net.
Just after the hour mark, Tadic gave Hugo Lloris his first test with a shot on the turn, but the France goalkeeper held it comfortably.
The game petered out as the substitutions mounted, and it will now be the results of M'Vila's expected scan that concern Blanc as much as the outcome here.