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Lacazette put the visitors 2-1 up on 37 minutes at the Stade Gaston-Gerard with his sixth goal already this season after Corentin Tolisso’s opener for Lyon had been cancelled out by a Frederic Sammaritano penalty.
But the 25-year-old, who on Thursday was recalled to the France squad for the start of their World Cup qualifying campaign, then hobbled off just before the break and was later seen with strapping and an ice pack around his left knee.
Things got worse for Lyon as Dijon came roaring back with goals by Julio Tavares, Dylan Bahamboula and Pierre Lees-Melou to claim their first points since returning to the top flight.
“I am worried. When a player comes off before half-time it is always worrying,” Lyon coach Bruno Genesio told Canal Plus at half-time before adding that the player would undergo tests on Monday to determine the extent of the problem.
Lyon do not play again until hosting Bordeaux in a fortnight but Lacazette must now be a major doubt for France’s upcoming matches in Italy and Belarus.
The situation is similar for Nabil Fekir, who was recalled to the national set-up for the first time since suffering a serious knee injury in France’s friendly win in Portugal alost a year ago.
But he came off in the second half and Lyon president Jean-Michel Aulas later revealed he may undergo minor knee surgery on Monday.
“We flouted the fundamental principles of football and were deservedly beaten. Losing Lacazette hurt us and we did not play as well in the second half,” said Genesio of the defeat.
OL had won their opening two league matches thanks to their star striker’s goals but were looking to do something they had not managed since 1981 by making it three straight victories to start a top-flight campaign.
They went in front in the 20th minute when Tolisso followed in to score after Baptiste Reynet in the Dijon goal had beaten away a Sergi Darder shot.
Dijon were level just four minutes later, however, as Sammaritano netted from the spot after Nicolas Nkoulou chopped down Tavares in the box.
The incident was a demonstration of the new application of the laws following the abolition of the so-called ‘triple punishment’ – last season Nkoulou would certainly have been sent off for denying Tavares the opportunity to score, but this time he was only booked.
Lyon were back in front as the lively Lacazette collected the ball on the edge of the box and fired a low left-foot shot into the bottom-left corner, but he then hobbled off.
And Dijon drew level again in first-half stoppage time as Tavares dived bravely in front of Lyon goalkeeper Anthony Lopes to head in a cross from the right by Sammaritano.
The Burgundy side had not even scored in their opening two games but they ran away with this match in the second half, going in front on 73 minutes when Bahamboula scrambled in from a corner.
They netted again towards the end as Lyon were unable to fully clear their lines from a corner and Lees-Melou, who had come off the bench for his top-flight debut, curled a beauty into the far corner.
Guingamp are the provisional leaders of the fledgling table after a 2-0 win at promoted Nancy, although they are level on points with Nice, who drew 1-1 at home to Lille.
Vincent Koziello put Nice ahead at the Allianz Riviera only for Lille captain Franck Beria to equalise with his first goal in Ligue 1 since November 2010.
Caen beat Bastia 2-0, Metz defeated Angers by the same score and Rennes came from behind to draw 1-1 at Montpellier.
Marseille recorded their first win of the season on Friday, beating Lorient 2-0 at the Stade Velodrome with Remy Cabella and Bafetimbi Gomis netting.
Champions Paris Saint-Germain will look to maintain their perfect start to the campaign when they visit Monaco on Sunday.