Frederick appeared inside CIA headquarters during the briefing on Proteo di Regno. He introduced himself and Carrie before telling everyone about Di Regno's heart, which contained dates about natural disasters. He then informed everyone that the next disaster would happen in forty-eight hours and that they needed to find a way to stop it.
After Brandon and the CIA found out that the weapon that could cause the disaster was in Cartagena, Jack and Brandon sent Vaughn, Sydney, and Dixon to Estrella Shipyard to intercept the device. While there, Dixon seemingly lost control over his emotions and threatened to kill himself and one of the guards with a bomb if he didn't tell him where the device was. Brandon ordered Vaughn to shoot Dixon so the bomb could be deacticated, but the bomb turned out to be harmless (Dixon had cut the primer cord). The Delta team Vaughn and the others participated in found the device thanks to Dixon, but it turned out to be an artificial version of Di Regno's heart. When the supposed disaster time came, nothing happened, and Brandon realized that Rambaldi was wrong. Jack then told Brandon that his time at the CIA was done, and that he'd be on a plane back to Washington D.C. (Countdown).
After an NSA facility was raided and several Rambaldi pieces were stolen, Brandon was brought back to CIA headquarters to explain himself. Brandon merely told Kendall that he didn't have the authority to tell everyone the information he knew. Furious, Kendall ordered for the remaining Rambaldi piece (Di Regno's heart) to be relocated to a neutral naval base. However, when Brandon and Jack were transporting the heart, they were ambushed by Sloane's men, and Brandon was one of the two agents killed in the crossfire (The Telling).