Cristiano Ronaldo missed his third consecutive training session on Friday with Portugal coach Fernando Santos pessimistic he will recover from a toe infection in time for the start of their UEFA Nations League title defence against Croatia.
The Juventus star, who has 99 goals in 164 international matches, is with the squad preparing for the match in Porto on Saturday but has not trained since Tuesday.
"I am very doubtful that by tomorrow (Saturday) he will be 100 percent OK," Santos told a press conference.
He said Ronaldo, 35, was continuing "gym work" having trained "very well" at the start of the week.
"Then suddenly (on Wednesday) one of his toes was red, as if he'd been stung by a bee," Santos reported, adding that Ronaldo was on a course of antibiotics after seeing a dermatologist.
"Now we have to wait. With an injury you can have an idea of how the recovery is going to take. With an infection you never know."
The five-time Ballon d'Or winner has not played since early August when Juventus were knocked out of the Champions League by Lyon.
He scored 37 goals in all competitions last season, a record for a Juve player, and insists he remains ambitious, laying out his season 'goals' on Instagram last week.
"Victories. Commitment. Dedication. Professionalism. With all my strength and with the precious help from my teammates and all of the Juventus staff, we work once again to conquer Italy, Europe and the World!" he wrote.
Portugal are returning to the city where as hosts they won the inaugural Nations League in June 2019, beating the Netherlands 1-0. Because Euro 2020 has been postponed a year, they also remain European champions.
After Croatia they face Sweden in Solna on Tuesday, with their group also containing world champions France.
Aside from Ronaldo both Portugal and Croatia will be without other star players.
The Portuguese football federation said that another member of the squad that won Euro 2016, Lille midfielder Renato Sanches, has been released from the squad for unspecified medical reasons.
Croatia, meanwhile, have excused Luka Modric and Ivan Rakitic from international duties against Portugal and for a World Cup final rematch with France on Tuesday.
Modric, who is 34, played a crucial role as Real Madrid rallied when La Liga resumed after the lockdown and was only rested when the title had been secured.
Rakitic, 32, was also a regular starter as Barcelona collapsed in the league in June and July, though he had been relegated to the bench for the Champions League quarter-final and the traumatic 8-2 loss to Bayern Munich. He has since been sold back to Sevilla for 1.5 million euros ($1.8 million).
With La Liga resuming on September 13, both wanted to extend their off-season breaks.