The 37-year-old all-rounder, a veteran of 321 one-day internationals, will be a significant loss to the Proteas as a batsman, bowler and on-field leader.
Kallis does not routinely play ODIs these days as part of a fitness programme, but he has been at the Indian Premier League and was expected to feature in the Champions Trophy.
Cricket South Africa have given no further details about the circumstances around Kallis' absence, but there was some good news to weigh against it with JP Duminy deemed fit for selection.
Duminy has been out for six months following nasty ankle and Achilles injuries sustained against Australia.
"Jacques' experience will obviously be missed but it does create an opportunity for David Miller, whose recent form has been most impressive," said selector Andrew Hudson. "It also gives a young player the chance to make his mark ahead of the ICC World Cup in 2015."
Hudson also welcomed Duminy back into the fold after confirming the 29-year-old's place in the 15-man squad, adding: "JP is well on the way to a full recovery. The latest information is that he will be fully fit to play his part in all three disciplines by the end of the month. He is a very experienced limited-overs cricketer and we don't anticipate his lack of match practice being any kind of problem.
"His return adds a lot of balance to the side and that, together with the presence of two batting all-rounders in Faf du Plessis and Farhaan Behardien, means that we now have the option to go into the tournament with seven specialist batsmen.
"As always there are unlucky players. Unfortunately we can only take 15 players to England. However, the World Cup is two years away in Australasia and is a wonderful incentive for those who have missed out to concentrate their focus."
South Africa Champions Trophy squad: AB de Villiers (captain), H Amla, F Behardien, JP Duminy, F du Plessis, C Ingram, R Kleinveldt, R McLaren, D Miller, M Morkel, R Peterson, A Phangiso, G Smith, Dale Steyn, L Tsotsobe.
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- Indian Premier League
- JP Duminy