Earlier this month, the same knee injury had forced him to retire from the US Open semi-final.
With Federer cutting the number of tournaments he plays - the Swiss only took part in events in Shanghai, Basel and the ATP finals after last year's US Open - Djokovic is now favourite to unseat Nadal as world number one.
But of more importance is Nadal's long-term recovery from a problem that has seen him miss long periods throughout his career.
Nadal's total points tally will drop to 7,660 over the coming weeks - 760 more than Federer and 1,215 more than Djokovic.
The Spaniard limped out of his semi-final at the US Open against Juan Martin Del Potro after receiving multiple on-court treatments for his ailing knee and being down two sets to love.More news: Willian scores victor as Chelsea beat PAOK Salonika
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"Although the discomfort in my knee is nothing new, we decided together with my medical and technical teams not to participate in the Asian tour so that the knee can recover in the way we want it to", he explained.
After visiting the doctor in Barcelona, Rafa chose to skip the Asian swing where he won 1100 points 12 months ago after lifting the trophy in Beijing and finishing runner-up in Shanghai and this means that Novak Djokovic is the favorite to finish the season as the year-end number 1 despite winning just six matches prior to Rome!
Nadal's time at the very top of the game looked to have been ended by a wrist injury in 2016 but he has confounded expectations to roar back and win three of his 17 Grand Slam titles.
He also reached the quarter-finals of the Australian Open this year, as well as the semi-finals at Wimbledon.