Key Yemeni General Ali Mohsen al-Ahmar, who is close to President Ali Abdullah Saleh, says he is backing the protest movement against the regime.
Two other army commanders are also reported to have resigned.
The announcement comes a day after the president dismissed his entire cabinet in apparent response to the protests against his rule. He asked them to stay in place in a caretaker capacity.
Meanwhile in the north, 20 people have been killed in fighting, reports say.