President Barack Obama said in a statement that he had accepted the resignation and thanked Bryson for the "invaluable experience and expertise" he brought to the administration.
Bryson, a 68-year-old former utility executive, served as a member of Obama's economic team and has advised him on energy issues. He said in a letter to the president that he was concerned his seizure "could be a distraction" from his performance as secretary and said the nation would be better served by "a change in leadership" at the department.
In a letter to Obama, dated Wednesday, Bryson made official his resignation and said it was a "consequence of a recent seizure and a medical leave of absence."
Earlier this month, Bryson transferred his functions and duties as secretary to Deputy Secretary Rebecca Blank, who is now acting commerce secretary.