Unseeded Naomi Osaka faces a tough first-round test as she returns to Paris a year on from her dramatic withdrawal after she was fined and threatened with a Grand Slam ban for refusing to honour media commitments.
Djokovic plays Yoshihito Nishioka of Japan in the first of 10 night sessions -- introduced at Roland Garros last year when a pandemic curfew saw most late matches played in front of empty stands.
It is the world number one's first Grand Slam match since his high-profile deportation from Australia. He won his first title of the year at the Italian Open earlier this month.
"I feel I am always in that contention to fight for any Grand Slam trophy," said Djokovic, who is seeded to meet Nadal in the quarter-finals and Spanish teenage sensation Carlos Alcaraz in the last four.
Djokovic's last match at a major was his loss to Daniil Medvedev in last year's US Open final, a defeat which denied the Serb a calendar Grand Slam.
Nadal has yet to win a title on his beloved clay this season, but played down concerns over the chronic foot issue that resurfaced in Rome.
"There is nothing to recover," said Nadal who faces Austalia's Jordan Thompson.
"What happened in Rome is something that happened very often in my practices."
"I was suffering after that for a couple of days, but I feel better. That's why I'm here."
Nadal began the year with a 20-match winning run, capturing a second Australian Open title to claim a record 21st Grand Slam and move ahead of Djokovic and Roger Federer.
The 35-year-old's record at the French Open stands at a staggering 105 wins and just three losses since his 2005 title-winning debut.
Djokovic has been responsible for two of those defeats. One came in the bruising semi-final 12 months ago, the most recent clash of the pair's epic 58-match rivalry.
All eyes on Swiatek, Osaka
Swiatek, the 2020 French Open champion, takes on Ukraine's Lesia Tsurenko in round one.
The 20-year-old from Poland has swept aside all-comers and transformed herself into the player to beat in women's tennis since the shock retirement of world number one Ashleigh Barty.
Swiatek has won her past five tournaments and is unbeaten in 28 matches dating back to Dubai in February. Her winning streak is the longest on the WTA tour since Serena Williams won 34 matches in a row in 2013.
"I'm aware that this streak is something that may be coming to an end soon, so I don't want to be like heartbroken when it's going to happen," said Swiatek.
Japanese superstar Osaka admitted she was "worried" over her return to the French Open, fearing she had "offended" people when she controversially quit the 2021 tournament.
Osaka, a former world number one and four-time major winner, then took a break from the sport, revealing she had been suffering bouts of depression.
"I'm not going to lie. Like when I first came here, I was very worried," the 24-year-old said last week.
"I was just kind of worried that there were people that I offended some way and I would just kind of bump into them."
She opens against American 27th seed Amanda Anisimova, a semi-finalist in 2019.
Anisimova knocked Osaka out of the Australian Open in the third round this year.
Reigning women's champion Barbora Krejcikova will play France's Diane Parry in round. The Czech world number two has been sidelined by arm injury since late February and is yet to play on clay this year.
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