Antoine Griezmann was on Monday ruled out of France's friendlies against Germany and Chile with an ankle sprain ending his record run of playing 84 consecutive games for Les Bleus.
The Atletico Madrid star will be absent from the French squad for the first time since November 2016 as France play their final friendlies before the Euro 2024 tournament from June 14-July 14.
Griezmann has appeared on the pitch for France in every match since a friendly against England in June 2017, when the forward was an unused sub.
Lazio's Matteo Guendouzi has been called up for the first time since the last World Cup in place of 127-cap Griezmann, who has scored 44 goals for France.
Coach Didier Deschamps has described Griezmann as "not irreplaceable but essential" for the France set-up, but accepted the recommendations of the team doctor, the French football federation said.
The 32-year-old missed four games for Atletico before returning last week and scoring in the Champions League against Inter Milan with the Spanish side advancing to the quarterfinals on penalties.
He also came on at halftime in the 3-0 defeat against Barcelona in LaLiga on Sunday.
"Antoine has a problem with his ankle, which reacted even though he played 45 minutes last night," Deschamps said.
Guendouzi has played seven times for France, scoring one goal. He last played in the final group match in the Qatar World Cup, a 1-0 defeat against Tunisia.
"With Antoine's qualities we're not going to find a player who has his characteristics," Deschamps said.
"A replacement position for position is very, very, very difficult to find. We will arrange things differently."
- 'Workforce review' -
AC Milan goalkeeper Mike Maignan is also an injury doubt while Paris Saint-Germain winger Ousmane Dembele is recovering from a punctured eardrum.
Deschamps said he was optimistic for Adrien Rabiot, Lucas Hernandez and Ibrahima Konate.
Liverpool defender Konate has not played the last three matches for the English club and was also absent for France in September and November due to injury.
"Ibou had some little niggling problems, he's coming off a season where he played a lot," said Deschamps.
For his final "workforce review" before revealing his European championships squad mid-May, Deschamps said he wanted "to involve as many players as possible".
The objective, he said, would be for the two-time European champions to anticipate what may happen in May or June because "we're never safe" from injuries.
"We are not here to try things, we know the players," he insisted.
However, Deschamps did not call up any newcomers, brushing aside speculation around 21-year-old PSG attacker Bradley Barcola.
"We're in rehearsal, to try different combinations in the two matches," Deschamps added.
France play two friendlies against European hosts Germany on March 23 in Lyon and Chile three days later in Marseille.
Deschamps' side then open their European campaign on June 17 in Duesseldorf against Austria.