De Jongh, the fifth centre to drop out of international contention in the last month, was admitted to hospital on Sunday and treated for pneumonia before he was discharged on Thursday.
He joins captain Jean de Villiers (knee), Frans Steyn (withdrew), Damian de Allende (knee) and Jaque Fourie (ankle) on the sidelines, leaving the Boks to start Saturday's first test against Wales with converted wing JP Pietersen at outside centre and Jan Serfontein, earning his first start, on the inside.
The team's medical staff said the severity of De Jongh's illness meant he had to be rested.
"Unfortunately this infection really takes a severe toll on the body and although he has recovered sufficiently, he has been advised not to participate in vigorous physical activity for the next three to four weeks," team doctor Craig Roberts said in a statement released by SARU on Friday.
De Jongh is the latest addition to a long list of injured players unavailable for selection against Wales in Durban on Saturday and a week later in Nelspruit, as well as a one-off fixture against Scotland in Port Elizabeth on June 28.
The others are Eben Etzebeth (foot), Pat Lambie (bicep), Frans Malherbe (concussion), Scarra Ntubeni (foot), Frik Kirsten (neck), Pieter-Steph du Toit (knee), Franco van der Merwe (ankle), Arno Botha (knee), Pierre Spies (bicep), Louis Schreuder (hand) and Gio Aplon (elbow).
(Reporting by Nick Said; Editing by John O'Brien)
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