Six-month-old Leah de Jager on Monday morning succumbed to a rare disorder that attacked her immune system.
She had been treated for severe combined immunodeficiency (SCID) at the Dora Nginza Hospital in Port Elizabeth since October last year.
On Monday, a Facebook support group that had been set up for Leah posted that she had passed away.
"Our hearts are sore but we know you are in the hands of Jesus," the post read.
"Everyone will miss you. You touched many people and you will leave deep footprints in our hearts."
Leah's father, Gerrit de Jager, 32, a radio DJ and entertainer, confirmed the news to Netwerk24.
News24 reported in October that the rare, life-threatening illness occurs in one-in-40 000 to 100 000 births and has a severe effect on children's immune systems.
De Jager told News24 at the time that Leah had become increasingly quiet when she was around three months old.
Outpouring of condolences
"My wife Lezaan and I googled her symptoms and found that many babies react the same way during growth spurts. We weren't really that concerned.
"But on October 6 she got a fever which didn't go away with treatment. We got her to a paediatrician who gave her one look and admitted her to hospital."
Leah was initially admitted to the Netcare Cuyler Hospital in Uitenhage, where she was treated for pneumonia.
"When she didn't respond to treatment, the doctor realised something was wrong."
After running blood tests, Leah was diagnosed with SCID and moved to intensive care.
Leah was then moved to the provincial government Dora Nginza Hospital, where she had been undergoing treatment.
By Monday afternoon, the news of Leah's death had elicited more than 1 100 Facebook comments from well-wishers.