Ronaldo and his partner announced they were expecting twins in October last year.
But late on Monday, the Manchester United forward revealed the twin girl survived during birth while the boy passed on.
Announcing the sad news on Instagram, Ronaldo said: "It is with our deepest sadness that we announce the passing of our baby boy. It's the greatest pain any parent can feel. Only the birth of our baby girl gives us the strength to live this moment with some hope and happiness.
"We would like to thank the doctors and nurses for all their expert care and support. We are all devastated at this loss and we kindly ask for privacy at this very difficult time. Our baby boy, you are our angel. We will always love you. Cristiano Ronaldo and Georgina Rodriguez."
Ronaldo and Georgina already have a daughter together, three-year-old Alana Martina, who was born in 2017.
The Manchester United striker also has twins, Eva and Mateo, from a previous relationship. His eldest son Cristiano Junior is the product of another relationship.
Ronaldo is one of the greatest footballers of all-time with five-Ballon d’ors to his name.
The former Real Madrid and Juventus forward is now international football’s greatest goalscorer, having found the net an incredible 115 times in 186 games.
Ronaldo led Portugal to glory in EURO 2016 and the inaugural edition of the UEFA Nations League in 2019.
He has scored 21 goals in 34 appearances across all competitions since returning to Old Trafford for a second spell at the start of this season.
