When Cole wants to become a surgeon, he tears up 17 of Lucy's cuddly horses and tries to re-assemble them.Lucy holds 17 individual funerals for them that Drew has to suffer through. It's happening again." Dave Franco portrays Cole Aaronson, a medical student at Winston University.

After his retirement, Kelso becomes more openly friendly with Dr Cox. He was not seen for the remainder of the season due to Neil Flynn leaving the show to go work on his own show The Middle. However, Lawrence asked Flynn if he would consider another part—the mysterious custodian who makes tormenting J. Elliot finally got through to her in the only way Denise understood — humiliating her — to get her to leave the hospital and blow off steam.

Neil Flynn portrays the hospital's custodian known as "Janitor" through most of the series. Flynn is an improv comedian and, as such, ad-libs many of his lines. In Scrubs: Med School, Denise had a main cast role as a teaching assistant at the new Sacred Heart.

As the season progresses, Lucy faces more and greater challenges in medicine and life. His family donated a large sum of money to get the new Sacred Heart Hospital built, and as such, Cole believes he is "untouchable" and can do whatever he wants.

In "Our Drunk Friend," she personally raises money to send an alcoholic patient to rehab, only to have it blow up in her face when he falls off the wagon. D., who had initially seemed to support her, tells her that he knew the patient was a lost cause, but felt that she needed to learn how to cope with defeat. While spoiled, arrogant, and immature, he occasionally reveals himself to have a good heart.

Kelso, who says, "Oh Perry, you are so edgy and cantankerous, like House without the limp." This is further explored in "My House," during which Cox acquires a temporary limp.

At the end of the episode, through a series of circumstances, Dr. Elliot is driven by a neurotic desire to prove her abilities to her family (in which all of the men are doctors), her peers, and herself. At the end of that season, she briefly leaves to take an endocrinology fellowship, which ends five days later after her research partner finds the cure to osteogenesis imperfecta, the disease they are researching. She tells Turk that if she were lucky enough to get married and have enough money to stop working, she would "walk out of this place and never look back." Judy Reyes portrays Carla Espinosa, the hospital's head nurse, who acts as a mother figure to the interns, often hiding their mistakes from their attending doctor.She loves horses and believes "if they could talk, they would be wise".Lucy is at first overwhelmed by life in a hospital, especially when both her chief professor, Dr.Cox, and her student advisor, Denise Mahoney (Eliza Coupe), take an immediate dislike to her.Seeking a respite, she sleeps with her classmate Cole Aaronson (Dave Franco), an arrogant rich kid who takes a naked picture of her without her knowledge and then humiliates her by letting it fall out of his backpack and into the wrong hands. D., who is temporarily teaching at the university; he takes her under his wing and encourages her to stand up to Dr. She continues an affair with Cole, who she says "[kills] her soul as he climbs into bed" with her.Ken Jenkins portrays Robert "Bob" Kelso, Sacred Heart's chief of medicine for most of the series.