Santos revealed the nature of Ronaldo's problem in his media conference ahead of the Croatia clash, confirming the infection was thought to have been caused by a bee sting.
Portugal had no issues in his absence at the Dragao, as Joao Cancel, Diogo Jota, Joao Felix and Andre Silva did the damage against a Croatia side that hardly threatened at all before Bruno Petkovic's consolation late on.
The UEFA Nations League's defending champion will hope to build on this win by beating Sweden next week, and could yet call upon Ronaldo, but Santos insisted that he was not resting the Juventus star.
"I wasn't resting him. If he was in good shape, he would have been [in the starting XI] able to play the game," Santos said.
"Today he trained, feels better and, at the moment, he will travel to Sweden. Then we'll see.
"There is no injury, but he has to recover from that infection."
To say it was Portugal's first match in 10 months, the Selecao was exceptional against the 2018 FIFA World Cup runner-up, which next faces France in a rematch from that Russia 2018 final.
Portugal peppered the Croatia goal in the first half and then eased to victory in the second period as it proved more clinical.
Santos was impressed, but stopped short of lavishing his team with praise. He had seen similar in training, therefore knew such a performance was possible.
"From what they did during the week, they showed me this was possible," he added. "This team knows each other well, the job was to remember what has been done before.
"The team corresponded, 100 per cent. There were some less good periods, but that is part of football."