The 32-year-old hooker has not played for his club since suffering concussion in the Six Nations defeat by Ireland at Twickenham last month which secured the Grand Slam for the Irish.
“I’m very disappointed that I will not be available for selection for Saints’ remaining Premiership games, as well as England’s tour to South Africa,” said Hartley.
“It has been recommended by specialists that I take a break this summer and while I find that decision hard to accept, it’s important I listen to that advice.
“I intend to use this time to recover fully from my injury, so I can be ready to hit the ground running when pre-season training starts later this summer.”
Hartley’s unavailability adds to England head coach Eddie Jones’s headaches as he tries to get England back on a winning track after an underwhelming defence of their Six Nations crown.
England are on a losing run of three ahead of the three Test series and will be without other key players such as Baths backs Anthony Watson, who has an Achilles injury, and Jonathan Joseph, who needs foot surgery.
Knee injuries, meanwhile, look set to remove lock Courtney Lawes and number eight Nathan Hughes from the tour which includes Tests on June 9, 16 and 23.
England last toured South Africa in 2012 losing the first two Tests before drawing the final match.