Picamoles has been a familiar face in the France national team since making his debut in 2008 – which was a 26–21 victory over Ireland during the 2008 Six Nations Championship. It was in 2008 that Picamoles scored his first try, against the Pacific Islanders on 15 November. Though part of the 2010 Six Nations Championship squad, Picamoles did not appear once in any of the five tests, in what turned out to be a Grand Slam campaign for Les Bleus. He was part of the 2011 Rugby World Cup squad that came runners-up to New Zealand, only playing in three tests during the tournament. After being dropped by Philippe Saint-André for most of 2014, a return to form with strong performances for Toulouse, saw Louis recalled to the French squad for the 2015 Six Nations Championship.