The 23 -- aged between 13 and 21 -- died in various places across the country's northeastern Mpumalanga province over the course of a week.
"We have opened 22 cases of murder and one of inquest," regional police spokesman Leonard Hlathi told AFP.
One of the deaths was labelled inquest because the boy reportedly had an existing health condition.
There have been no arrests yet as police compile statements and await post-mortem results.
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Deaths at so-called initiation schools in South Africa are common, with several hundred cases recorded in recent years due to bleeding and infections.
Boys spend around a month in secluded bush or mountains areas for the sessions that also include lessons on the virtues of masculine courage and discipline.
There are usually two circumcision seasons - in winter during the months of May through July and in summer between November and December.
Government and the ruling African National Congress Party have expressed concern at the deaths which have nonetheless sparked little public outrage.