“The national team captain… has an infection in his right foot and is undergoing treatment with antibiotics,” the Portuguese FA said in a statement.
Ronaldo, 35, was restricted to a gym session on Wednesday.
Lille midfielder Renato Sanches has been ruled out of his country’s first two Nations League games with an undisclosed injury.
European champions Portugal won the inaugural Nations League last year, beating the Netherlands 1-0 in the final in Porto.
They begin the new campaign at home to Croatia on Saturday before travelling to Sweden three days later.