The footage, shared by CNN-affiliate BFM, showed Macron walking up to a metal fence and clasping the arm of a man in the crowd as he began to greet onlookers in the village of Tain-l'Hermitage, in the Drme region of France.
The man, while gripping Macron's arm, then slapped the president across his left cheek while yelling for the end of "Macronie" -- a pejorative term used in the French press for Macron's presidency.
Macron's security detail quickly intervened, tackling the man while pulling the president away from the metal barrier.
"A man indeed tried to hit the President of the Republic," the Elysee said in a statement to CNN. "We have no further comments at this point. Exchanges with the crowd and handshakes resumed. The trip continues."
Moments before slapping Macron, the perpetrator also shouted, "Montjoie! Saint-Denis!," a medieval battle cry used by the Capetian royal dynasty, which ruled France from the 10th to the 18th century.
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The motto is also widely known in France for being a line from 1993 fantasy comedy film Les Visiteurs, in which a 12th-century knight and his squire magically travel in time to the 90s and find themselves adrift in modern society.
Two 28-year-old men, including the man who slapped Macron and another accompanying him, were placed in police custody at 1.45 p.m. local time for alleged violence against a person holding public authority, the prosecutor's office of the city of Valence told CNN.
Far-right leader Marine Le Pen, who is Macron's biggest political opponent, said physically attacking the president was "unacceptable," during a Tuesday press conference.
"We can attack him politically" but any violence against him should be condemned in a democracy, she added.
Macron was in the area to meet restaurant owners, ahead of Wednesday's easing of COVID-19 restrictions in France.
Macron is currently on a charm offensive, with France's presidential elections less than a year away and the country just weeks from regional elections on June 20 and June 27.
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At the end of April, the president told regional press that he wanted to "go to the regions to take the pulse of the country, to get in contact with people." His political opponents say these presidential outings are actually campaign trips.
Macron is not the first French politician to be slapped in the face while shaking hands.
In January 2017, former Prime Minister Manuel Valls, who was at the time the left-wing candidate in the presidential primary, was visiting Lamballe in Brittany when a young man struck him before being overpowered by the security services.
Valls was Prime Minister between 2014 and 2016 under President Franois Hollande.
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