The Spaniard has won on the red clay of the Foro Italico, normally played in May but which starts behind closed doors in Rome on Monday, a record nine times, including the last two editions
Rafael Nadal returns to competition after a six-month break chasing a tenth Italian Open title in Rome against his greatest rival Novak Djokovic before his bid for a 13th Roland Garros crown later this month.
The Spaniard has won on the red clay of the Foro Italico, normally played in May but which starts behind closed doors in Rome on Monday, a record nine times, including the last two editions.
World number one Djokovic, a four-time Rome winner and five-time runner-up, lost to Nadal last year in the final.
The 33-year-old is the top seed ahead of world number two Nadal, in the tuneup for the final Grand Slam of the season at the French Open which begins on September 27.
Djokovic won the French Open in 2016, with Nadal having won the last three titles since.
Nadal, 34, has not played since winning in Acapulco at the end of February, skipping the US Open over coronavirus concerns.
Djokovic tested positive for coronavirus in June after an exhibition tournament he organised, but the Serb won his 80th career title at the Cincinnati Masters last month.
He also captured his 35th ATP Masters crown, matching Nadal's all-time record, with the pair battling to pull ahead in Rome this week.
Djokovic arrives in Rome after his bid for an 18th Grand Slam ended amid controversy at the US Open a week ago when he was disqualified after accidentally striking a female line judge with a ball during his last-16 match.
Nadal opens his Rome challenge on Wednesday against 27th-ranked fellow Spaniard Pablo Carreno Busta, the recipient of a first round bye, after his run to the US Open semi-finals.
Nadal could play either Greek third seed Stefanos Tsitsipas or seventh seeded Italian Fabio Fognini for a place in the final.
Nadal has a 61-6 tournament record, having not lost before the quarter-finals since 2008.
Djokovic will start against either Italian Salvatore Caruso or a qualifier, with a potential semi-final clash against France's fifth seed Gael Monfils or tenth seeded Swiss Stan Wawrinka.
US Open finalists Dominic Thiem and Alexander Zverev, the 2017 winner, both pulled out after their runs in Flushing Meadows, with injured Roger Federer also sidelined.
Former French Open champion Simona Halep headlines the women's event which also includes defending champion Karolina Pliskova and two-time Rome winner Elina Svitolina.
Serena Williams withdrew due to a left Achilles tendon injury sustained in her US Open semi-final defeat.
The former world number one, a four-time Rome champion, joined 2019 US Open winner Bianca Andreescu and two-time Wimbledon winner Petra Kvitova in skipping the Italian event which will also be without world number one Ashleigh Barty and newly-crowned US Open champion Naomi Osaka.
World number two Halep won the Prague title a month ago, and will face either Anastasija Sevastova or Jasmine Paolini in the second round.
Former French Open champion Garbine Muguruza opens against American Sloane Stephens.
Venus Williams, the 1999 Rome champion, has a tough start against US Open finalist Victoria Azarenka, with the winner taking on third seeded Sofia Kenin.
Dutch player Kiki Bertens and Swiss Belinda Bencic are among the six top ten players in the field.