Sheikh Mohammed's eldest son, Sheikh Rashid bin Mohammed bin Rashid Al Maktoum, has died at the age of 34.
The United Arab Emirates' state news agency WAM said the son of Dubai's ruler died of a heart attack.
Sheikh Rashid was an avid sportsman and racing enthusiast, running horses in Dubai under the Zabeel Racing International banner.
His best horses include top-class sprinter Reynaldothewizard and Group Two winner Surfer.
The ruler's court has declared three days of mourning.