The 50-year-old comedian had planned to complete 27 marathons in 27 days to reflect the number of years former South African president Mandela spent in prison.
However, after four days he took to his Facebook page to announce he was pulling out of the effort for the time being, citing "unforeseen medical complications".
Izzard blamed "a multitude of factors including severe terrain, humidity and altitude".
"I owe that to Nelson Mandela who has inspired the world to struggle and succeed no matter what obstacles are thrown at us."
Back in 2009, Izzard - a seasoned runner - finished 43 marathons in 51 days for Sport Relief.