Jack Leach will return home from South Africa with immediate effect after battling multiple health issues.
The left-arm spinner has failed to recover from sepsis that he contracted during the New Zealand tour in November and has additionally been hit by bouts of flu and gastroenteritis ahead of the first Test against South Africa.
The Somerset star was replaced with Dom Bess in the previous Test, which England won in an enthralling contest on the final day.
Leach, who also suffers from Crohn's disease, "has not been able to reach the expected levels of fitness to be considered for selection" according to the statement released by England and Wales Cricket Board.
The bespectacled player last bowled a competitive delivery two months ago and is hoping to get fit in time for the Sri Lanka series.
“It has been an unfortunate time for Jack with illness and since the Test series in New Zealand six weeks ago, he hasn’t been able to get 100 percent fit,” said England head coach Chris Silverwood.
“This has hampered his preparation in South Africa and despite his best endeavours he is not in a position to make himself available for selection for the final two Test matches."
Leach's bowling heroics in England's win over Sri Lanka in 2018 made him a regular in his side's Test unit.
He then became a cult hero for his stubborn resistance in a last-wicket stand alongside Ben Stokes amidst England's memorable in the third Ashes Test at Headingley last year.
“He is a great lad to have around the squad and his infectious personality and popularity will be missed. However, his focus has to be getting himself better and receiving the optimum levels of recovery and treatment, which is best served back in England without any distractions," Silverwood added.
“I have no doubt that he will return to full fitness in the medium-term and hopefully he will recover in time for our tour of Sri Lanka in March."
England were able to draw level with South Africa in Newlands after the visitors faced a massive defeat in Centurion.
The third Test of the four-match series will take place in Port Elizabeth starting January 16.