After becoming the first man since Rod Laver in 1969 to win four straight majors - he capped the achievement at Roland Garros 12 months ago to complete the career grand slam - Djokovic slumped badly by his standards. "Andre (Agassi) has left already".
Having fired his entire coaching staff earlier this year, the 30-year-old is hoping that former tennis star Andre Agassi will be able to rectify what's been ailing him.
The Serbian looked composed throughout the first set, but encountered some trouble in the latter stages of the second set.
Djokovic, trying to become the first man in the Open era to win all four majors on at least two occasions, won the contest on Court Philippe Chatrier after two and a half hours. Djokovic split from his long-time team last month as he sought answers to the slump that has seen him struggle since adding a fourth consecutive grand slam title here past year.
"It's incredible to have Agassi in my team, every day is special with him, everyday I'm learning something new", said Djokovic, who split with longtime coach Marian Vajda at the start of the month.
"I'm very happy to be back here after what happened a year ago".
On the women's side, Garbine Muguruza opened her title defense by beating Francesca Schiavone 6-2, 6-4.
Talking about Nadal, Nick Bollettieri had some doubts about the physical condition of the Spaniard: "The only question I would have about Nadal is how he would react to seven matches, best of five sets".
Agassi, the 1999 Roland Garros champion and eight-time major victor, had only committed to just a "few matches" with the world number two.
Schiavone again responded but Muguruza broke to lead 5-4 and came through a long final game to set up another tricky match against Estonia's Anett Kontaveit, one of the form players of the clay season.
If the Spaniard can build on his encouraging start - a 6-1, 6-4, 6-1 win against the French world No45, Benoît Paire, on Court Suzanne Lenglen in one hour 52 minutes - he is headed for a semi-final collision with Djokovic. "But it's hard to say whether there is significant difference on the court, because it's only a few days that we are together".
In the end it wasn't the most sublime we've seen Djokovic on the terre battue, but the effort was certainly something to build on. "So I'm happy with that, and it gives me a little more freedom to spend more time working on my game tomorrow and playing hopefully even better on Wednesday". Then he came to Roland Garros and endured a first-round exit at the clay-court Grand Slam tournament for the first time, losing as the No. 14 seed to Jiri Vesely of the Czech Republic 7-5, 7-5, 6-3 on Monday.
- Terror attacks are not going to scare us away, say Ariana fans
- May, Corbyn clash over Brexit plans with UK vote 1 week away
- More than 1500 injured in panic after soccer game
- Portland stabbing suspect said 'that's what liberalism gets you': court papers
- Apple's iOS 11 Comes With New Do Not Disturb While Driving Mode
- Analyst group: IS claims London attack
- Kashmir under curfew after Sabzar Bhatt killing, separatist Yasin Malik arrested
- Six killed, 48 hospitalised in London terror attack
- Meeting with Abbas, Trump calls Manchester attackers 'evil losers'
- Three Mile Island owner threatens to close ill-fated plant