Sioux Falls General Hospital is a hospital located in Sioux Falls, South Dakota.
After the Escape of the Leviathans, the Leviathan known as Annie came to the hospital and consumed the real Dr. Gaines, taking on his form in order to give the Leviathans a discreet source of food, having gotten the idea from watching Dr. Sexy, MD. Now known as Dr. Gaines, the Leviathan helped two others replace the head nurse and the hospital administrator, but was witnessed consuming a patient's organs by Sheriff Jody Mills who had been at the hospital for an appendectomy. Jody contacted hunter Bobby Singer who helped Jody escape the hospital and confronted Dr. Gaines in the morgue, but could not hurt him.
After a battle with Edgar, Sam and Dean Winchester were taken to the hospital for treatment when their injuries proved to be serious enough for Dean to get medical attention. Dean's broken leg and Sam's head injury were treated, but the three Leviathans at the hospital learned of their presence and attempted to kill the Winchesters. With the help of Bobby who stole an ambulance, the Winchesters managed to escape the hospital without further injury. Bobby would later report that the three Leviathans failed to return to work at the hospital after the escape and had vanished.
Six years later, Alex Jones was working at the hospital as a nursing assistant while occasionally helping Jody with hunting. In an attempt to find Kaia Nieves, Claire Novak visited Alex at work where Alex learned that a Jane Doe matching Kaia's description had just been admitted with a concussion and dehydration. Attempting to flee the hospital, Kaia was confronted by one of the Cloaked Figures outside, but it was killed by Claire with Jody's help. Afterwards, Kaia agreed to go with Claire and Jody.