Djokovic is bidding for a seventh title at the All England Club to move level with US great Pete Sampras.
Nadal, fresh from a 14th French Open victory and a record-extending 22nd major, is halfway to the first men's calendar Grand Slam in more than half a century.
The season's third Slam tournament has already made political waves even before the first ball is served on Monday.
The decision to ban Russian and Belarusian players in the aftermath of the invasion of Ukraine means there is no place for world number one Daniil Medvedev or eighth-ranked Andrey Rublev.
Both the ATP and WTA, who control the men's and women's tours, retaliated by stripping ranking points from the tournament.
For the first time since his debut in 1999 -- notwithstanding the Covid-cancelled 2020 edition -- Federer will be a no-show as the 40-year-old recovers from knee surgery.
Also missing is Germany's world number two Alexander Zverev, who suffered serious ankle ligament damage in an horrific injury in his French Open semi-final against Nadal.
However, Medvedev and Zverev have never shone at Wimbledon with neither man making it past the fourth round.
Djokovic and Nadal, ranked three and four, are the top seeds meaning if they are to face each other for the 60th time, it can only be in the final.
- 'I love Wimbledon' -
Djokovic, the champion in 2011, 2014, 2015, 2018, 2019 and 2021, could be playing in his final Slam of the year.
His refusal to be vaccinated is likely to rule him out of the US Open later this year.
A bruising quarter-final loss to Nadal at the French Open which saw him deposed as champion in Paris will also likely provide extra motivation.
Nadal won the last of his two Wimbledon titles in 2010 having captured his first with an epic triumph over Federer two years earlier.
The 36-year-old Spaniard arrives at Wimbledon with the Australian and French Opens secured.
He is halfway to becoming only the third man -- and first since Rod Laver in 1969 -- to complete a calendar Grand Slam.
Nadal has endured a bittersweet relationship with Wimbledon.
Two titles have been accompanied by three lost finals as well as injury-enforced absences in 2004, 2009, 2016 and 2021.
There remains a question mark over his durability for the two weeks at Wimbledon having played the entire French Open with his troublesome left foot anaesthetised.
Nadal has since undergone a course of radiofrequency stimulation, a treatment aimed at reducing nerve pain in his foot.
"I love Wimbledon," said Nadal. "I had a lot of success there. A player like me, I am always ready to play Wimbledon."
- Berrettini waits -
Should Djokovic or Nadal fall, then Italy's Matteo Berrettini, runner-up to Djokovic in last year's final, would be the most likely beneficiary.
World number 11 Berrettini has won back-to-back grasscourt titles at Stuttgart and Queen's.
"I don't know if I'm the favourite as Novak and Rafa (Nadal) are always there; Rafa has already won two Slams and no-one expected him to win in Australia," said 26-year-old Berrettini of his Wimbledon chances.
"I don't feel like I'm the favourite but I know I can do it, I can't pull the wool over people's eyes."
Of the remaining top 10, French Open runner-up Casper Ruud has lost in the first round on his two previous trips to Wimbledon.
Stefanos Tsitsipas has fallen at the first hurdle three times out of four while Spanish teen star Carlos Alcaraz only made his main draw debut in 2021, reaching the second round.
Felix Auger-Aliassime made the last-eight last year while 10th-ranked Hubert Hurkacz, the champion on grass in Halle last weekend, was a semi-finalist in 2021.
On the way, the Polish player defeated Federer in the quarter-finals which was the Swiss star's last appearance on the tour.
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