Hartley suffered a blow to the head in last month's Six Nations loss to Ireland and has not played competitively since.
On the grounds of specialist medical advice, the 32-year-old will now take an extended break from the sport to make sure he has enough time to recover.
It is not the first time Hartley has been prevented from touring with England because of concussion, as he suffered the same fate in 2016 before Eddie Jones' men jetted off to Australia.
"It has been recommended that I take a break this summer and while I find that decision hard to accept, it's important I listen to that advice," he said.
He is said to be 'very disappointed' at missing the tour but is looking to recover in time for the start of next season.
England face the Springboks in three Tests, starting in Johannesburg on June 9, and already have a number of injuries to contend with.
Bath duo Anthony Watson and Jonathan Joseph are out of the tour with achilles and foot injuries respectively, while Courtney Lawes and Nathan Hughes were ruled out last month due to injury problems.