Bryson said in his resignation letter to US President Barack Obama that his health problem could be a distraction from his work and might affect his performance as a minister.
"I have concluded that the seizure I suffered on June 9 could be a distraction from my performance as secretary and that our country could be better served by a change in leadership of the Department," Bryson wrote.
The letter sent to Obama on Wednesday night was released to the press.
In a letter to the employees of the Commerce Department, Bryson who had taken a leave of absence after the June 9 incident, said he is resigning.
"The work that you do to help America's entrepreneurs and businesses build our economy and create jobs is more important now than ever and I have come to the conclusion that I need to step down to prevent distractions from this critical mission," Bryson said.
In a statement, Obama said he had accepted the resignation, and praised him as a distinguished leader.
"I want to extend my deepest thanks and appreciation to John for his service over the past months, and wish him and his family the very best," he said.
Obama said as secretary, Bryson fought tirelessly for US businesses and workers, helping to bolster its exports and promote American manufacturing and products at home and abroad.
As commerce secretary, Bryson led his first trade mission to India from March 25 to 30.
