The 24-year-old missed training in Los Angeles ahead of the match, with Belgian officials confirming he would not be included in Rudi Garcia's squad as the Red Devils look to build on their opening 1-1 draw against Egypt.
"Due to illness, Jeremy Doku will not be part of the squad for our upcoming game against Iran," Belgium announced on social media.
Doku's absence is a significant blow for a Belgian side seeking momentum in a tightly contested group. All four teams in Group G remain level on one point after the opening round of fixtures, making Sunday's encounter particularly important in the race for a place in the knockout stages.
Reports in Belgium suggest Doku has been battling a recurring respiratory infection for several weeks. Although he travelled to the United States with what was initially described as a severe cold and showed signs of improvement during the second half against Egypt, his condition reportedly worsened following a difficult night in Los Angeles.
After consultations with medical staff, Belgium opted not to risk the winger and instead placed him on a course of antibiotics in the hope he will recover in time for the final group-stage match against New Zealand.
"It is better to let him rest now and then work towards the last group match against New Zealand," said Belgian sports director Vincent Mannaert.
Garcia must now find a way to replace one of his most dangerous attacking players. Doku's pace and ability to beat defenders one-on-one have become key components of Belgium's attack, and his absence is expected to trigger a reshuffle in the forward line.
Leandro Trossard could move into his preferred role on the left wing, while Dodi Lukebakio, Alexis Saelemaekers and Charles De Ketelaere are among the contenders to fill the vacancy on the opposite flank.
Doku started against Egypt but struggled to make a major impact before being replaced by Matias Fernandez-Pardo late in the match.
The illness setback comes during a period in which the winger has also found himself at the centre of debate away from the pitch. Earlier this week, Doku revealed he intends to leave Belgium's World Cup camp temporarily if necessary to attend the birth of his first child.
His wife, Shireen, is expected to give birth during the second week of July, potentially coinciding with the latter stages of the tournament should Belgium progress.
"It's my first child, so I would definitely want to be there," Doku told Reuters. "Nobody wants to miss the birth of their first child. But I also know that football involves many other considerations."
While many supporters praised the player's stance, his comments sparked criticism from French television presenter France Pierron, who questioned the decision to potentially leave the tournament during a World Cup campaign.
The remarks generated a strong backlash online, with former Olympic boxing champion Brahim Asloum among those defending Doku.
"A baby is your entire life. A World Cup is over when it is over," Asloum wrote on social media.
Pierron later issued an apology, saying her comments reflected a personal opinion expressed during a heated discussion and were never intended to diminish the role fathers play in supporting their partners and newborn children.
For now, however, Belgium's focus remains firmly on Iran and the hope that Doku's absence will be limited to a single match. With the group finely balanced and qualification still wide open, the Red Devils will be eager to secure three points before turning their attention to a potential return for one of their brightest attacking talents.