Dr. Natalie Manning is a pediatrician at Gaffney Chicago Medical Center, who is doing a fellowship in emergency medicine. It was revealed in the first episode that her husband, Jeff, was killed in action. She was also in her third trimester at the beginning of the show. Later, she gave birth to a beautiful boy and named him Owen.
In Season 2, she enters a relationship with her late husband's best friend, Jeff Clarke, but she later ends it after Jeff reveals a secret in 2x09. In 2x14, she and Dr. Halstead have to make their patient to make a decision as to whether the woman's nephew or son should receive the blood transfusion. Dr. Manning also forms a friendship with Dr. Halstead's brother: Detective Jay Halstead, who is sometimes called to the hospital if it is discovered that a crime has been committed. Natalie and Dr. Halstead soon begin to grow closer, but Will's girlfriend, Nina Shore, begins to get jealous. In 2x22, Natalie gets a haircut and meets Will and Jay at Molly's. In 2x23, Natalie invites Jay to Noah Sexton's graduation party, but Jay declines. At the party, Will dances with Natalie.