The French delegation of 50,000 will be beaten only by Italy with 85,000 attendees. The French contingent will be accompanied by 82 bishops.
Despite being called World Youth Day, the event actually spans five days, from August 16th to 21st, and will include a visit from Pope Benedict XVI.
Around a million participants are expected at the event, which is held every three years. The last event was in Sydney in 2008.
"Everything I've heard says it will be an unforgettable experience," 18-year old Anne-Claire told regional newspaper Ouest France. She will travel with 30 other young people from the town of Vitré, east of Rennes in Brittany.
A survey conducted for religious magazine La Vie says the average age of attendees from France is 20 with women making up 56 percent of the delegation.
The poll said 54 percent of the people questioned go to church once a week. This compares to a national average in France of just 4 percent in the 18 to 25 age group.
When asked the main reasons for attending the Madrid event, the most cited were to "meet other christians", "reinforce my faith", "have a good time" and "show the world the importance of the catholic church."
Madrid will be a busy place in mid-August as demonstrations against economic hardship continue. On Thursday night at least 20 were injured, including seven police officers, in clashes between protestors and riot police.