Sa'id took part in the defense of Uthman's house when it was besieged by Egyptian rebels in 656. The caliph was ultimately killed and Sa'id was wounded in the attack. In the aftermath, he was set to join Aisha, Talha ibn Ubayd Allah and Zubayr ibn al-Awwam in their pursuit of vengeance over Uthman's death. However, he refused to fight alongside them against Uthman's successor, Caliph Ali () at the Battle of the Camel. Instead, he settled in Mecca. Despite not participating in the war with Ali, Caliph Mu'awiya I (), a leading opponent of Ali, appointed Sa'id governor of Medina in 669. He replaced Marwan ibn al-Hakam until the latter was reappointed to the post in 674.