Media reports said the Serbian star had pulled out of the tournament and he was not included in the draw on Monday.
He is yet to win a title this season and has only played in four tournaments this year, having decided to lighten his schedule.
Veteran tennis great Rafael Nadal (37) will continue his comeback from injury in Madrid and has been pitted against 16-year-old American Darwin Blanch in the first round.
Djokovic has now pulled out of the Madrid Open three times in four years.
The Serbian could still appear in Rome at the Italian Open before defending his French Open title from May 26th.
Djokovic is a three-time champion at the two-week clay court event in the Spanish capital.
It is his second Masters 1000 withdrawal this year after skipping the Miami Open in March.
Djokovic attended Real Madrid's 3-2 win over Barcelona at the Santiago Bernabeu on Sunday and is expected to appear at the Laureus Awards in Madrid on Monday, where he is in contention to win the Sportsman of the Year trophy.
Veteran tennis great Nadal played at the Barcelona Open but was defeated in the second round by Alex de Minaur in straight sets.
If he defeats teenager Blanch then he will face Australian world number 11 De Minaur in the second round for the second week in a row.
Reigning champion and second seed Carlos Alcaraz said he was hoping to be fully fit to play in Madrid after a forearm problem and will face either Alexander Shevchenko or Arthur Rinderknech in the second round.
Jannik Sinner, second in the world rankings and top seed in Djokovic's absence, will face either Italian compatriot Lorenzo Sonego or a qualifier in the second round.
