Yes, Blair and Serena were friends. They met in high school and became close after Serena moved to New York to live with her father. The two girls bonded over their shared love of fashion and shopping, and they remained close even after Blair started dating Nate Archibald. However, their friendship was always tumultuous, and they frequently fought over Nate, among other things. In the end, though, they always managed to patch things up and remain friends.