Recurring
Dylan Kingwell (season 1, 3 and 6), Logan Pierce (guest season 3) and Miles Marthaller (guest season 7) as Steve Murphy: Shaun's late younger brother, in flashbacks and later dreams and visions. He also portrays Evan Gallico, a boy in the present (Season 1) that resembles Shaun's brother and is suffering from stage 4 osteosarcoma.
Elfina Luk as Nurse Dalisay Villanueva. In season 5, she is revealed to be domestically abused by her partner Owen, which makes her fail to catch up to her shifts. At the end of season 5, she is stabbed by Owen, but Andrews and Glassman manage to save her life. Owen is arrested for her attempted murder, but he expresses remorse for his actions to Asher Wolke, almost committing suicide by cop out of guilt. She is shown to have fully recovered and returned to work by the time of Lim's return three months later. In season 6, she and Andrews develop a romantic relationship.
Teryl Rothery as Dr. Jan Lancaster (seasons 1–5, 7), an anesthesiologist and one of the doctors who is often seen helping out in surgery. In "Claire", her full name is given as Jan Lancaster.
Marsha Thomason (season 1) and Golden Brooks (guest season 6) as Dr. Isabel Barnes, a doctor at St. Bonaventure and the ex-wife of Andrews. In season 1, they are shown to have trouble having kids and go to a therapist for help. At the end of season 4, during the trip to Guatemala, Andrews reveals that he and Isabel are getting a divorce as she is seeing someone else. In season 6, she returns to take over the case of a woman pregnant with sextuplets.
Eric Winter as Dr. Matt Coyle (season 1), an attending surgeon who sexually harasses Claire when they work together on a case, resulting in Jared getting fired when he finds out and assaults him. He is also revealed to have done the same to other female employees who haven't spoken against him out of fear of risking their jobs. Without any evidence of his actions, Coyle is transferred to another department and two of his former residents, Morgan Reznick and Alex Park, are incorporated into Melendez's team. Jared also files a lawsuit against the hospital for racism when they refuse to rehire him, which he wins, but ends up losing the respect of Melendez and Andrews in the process.
Chris D'Elia as Kenny (season 1): Shaun's new neighbor, who moves into Lea's apartment. Shaun mentioned that he was arrested when Lea returned.
Kirby Morrow (season 1) and Michael Trucco (guest season 3 and 7) as Ethan Murphy, Shaun's abusive father. In season 3, he is reunited years later with his son when he is diagnosed with terminal pancreatic cancer to make amends, but after Shaun forgives him, Ethan throws hurtful words at Shaun before succumbing to his cancer thirty minutes later.
Rebecca Husain (season 1), Joanna Going (guest season 3) and Patricia Cullen (guest season 7) as Marcie Murphy, Shaun's mother, who despite loving her son, never did anything to help Shaun and stand up to her abusive husband. In season 3, she is reunited with Shaun years later when Ethan is diagnosed with terminal pancreatic cancer. She ends up becoming a widow after Ethan dies, and Shaun cuts her out of his life for good. In season 5, after Shaun and Lea get engaged and start mailing the invitations for their wedding, Lea decides against inviting Marcie, not wanting Shaun to be reminded of his traumatic past.
Sheila Kelley as hospital barista Debbie Wexler (seasons 1–4), a love interest for Dr. Glassman and later his fiancée and wife. After getting fired in the third season, she becomes Glassman's office manager. In season 4, they separate after a series of arguments. In real life, Kelley is married to Richard Schiff, who plays Glassman.
Lisa Edelstein as Dr. Marina Blaize (season 2), an oncologist
Holly Taylor (season 2) and Audrey Wise Alvarez (guest season 1 and 6) as Maddie Glassman, Aaron's estranged daughter who died of a drug overdose at 19.
Daniel Dae Kim as Dr. Jackson Han (season 2), is a Neonatal Cardiac Surgeon and former Chief of Surgery of San Jose St. Bonaventure Hospital, who had trouble with Shaun's behavior and autism, especially his inability to communicate. Against Shaun's wishes, he has him transferred to Pathology where he can help patients without interacting with them, but Han fires him when he keeps on demanding his old job as a surgeon back. Andrews, as president of the hospital, eventually fires Han to save Shaun, but gets himself fired as well. Lim takes over his vacant position in season 3 and rehires Andrews as an attending surgeon.
Sharon Leal as Breeze Browne (season 3; guest season 1–2), Dr. Claire Browne's mother who has bipolar disorder. She dies in a car crash in the season 3 episode "Claire."
John Patrick Amedori as Dash Snyder (season 3; guest season 2), the husband of Claire's best friend and former college roommate Kayla. After Kayla dies from terminal ovarian cancer, he and Claire go out on a date, which were Kayla's final wishes when she first came to the hospital, but she doesn't reciprocate his feelings and eventually realizes she is in love with Melendez.
Ricky He as Kellan Park (season 2–4), Dr. Park's estranged son
Karin Konoval as Donna Petringa (season 2–4), a scrub nurse at St. Bonaventure who is often seen assisting in surgeries or monitoring patients. She dies of COVID-19 in "Frontline Part Two" in season four. She has been a nurse for forty years and has a son and granddaughter.
April Cameron as Alyssa Hawks (seasons 3, 5–7; guest, season 4), a young nurse who works at the hospital. As revealed in season 6, she suffered from an addiction of some sort in the past as she attends Danny Perez's NA meeting.
Brian Marc as Dr. Enrique "Ricky" Guerin (season 4): One of the new surgical residents who has a laid-back attitude and is polyamorous. He is assigned as one of Claire's junior residents. Enrique eventually decides to leave St. Bonaventure in order to join a program that will allow him to help out in needy areas of the world.
Summer Brown as Dr. Olivia Jackson (season 4): One of the new surgical residents coming from Chicago initially who is double majoring in neonatal and Pediatric oncology. Her parents are also both surgeons. Olivia has both an MD and PhD from Harvard. She is also secretly the niece of Dr. Marcus Andrews. She is one of Shaun's junior residents before getting herself fired after falsely taking credit for leaking patient information, having never actually wanted to be a doctor in the first place.
Marcuis Harris as Miles Brown (season 4), Claire's absentee father shows up out of nowhere in episode 13 of season 4: "Spilled Milk." In episode 18: "Forgive or Forget", they start to patch things up and form a relationship.
Rachel Bay Jones as Salen Morrison (season 5), who buys St. Bonaventure at the start of season 5 through her corporative Ethicure company. She is described by executive producer David Shore as an "internal nemesis". In "Cheat Day", after firing nearly all of his colleagues for going against her, Andrews manages to convince her to stand down and she signs off the Ethicure ownership.
Hollis Jane Andrews as Sophie (season 5), a documentarist with a form of dwarfism who takes an interest in Shaun and Lea
Giacomo Baessato as Jerome Martel (season 5–7), a male nurse who begins dating Asher. As revealed in "Second Chances and Past Regrets", he has been HIV-positive for years. In "Who at Peace", he intended to propose to Asher, who was killed by two anti-semites that very same night. In the series finale, he is shown to have moved on from Asher's death and married another man.
Savannah Welch as Dr. Danica "Danni" Powell (season 6), one of the new residents in season 6. She is a former US Navy Lieutenant who lost her right leg following a flight deck accident. In "The Good Boy", especially due to her constant pattern of disobedience, she is fired after an unauthorized surgery to save her friend on parole Vince, which she had dragged Asher into, who gets a two-month probation, along with Perez for his relapse.
Michael Patrick Thornton as Dr. Clay Porter (season 6), a disabled pediatrician whom Powell sets Lim up with. They start a relationship and proposes to Lim, only for her to turn him down and suggest they move in together instead. In season 7, it is revealed that because of Lim's indecisiveness to marry Clay, he broke off the relationship and moved to Chicago for a fellowship.
Kayla Cromer as Charlotte 'Charlie' Lukaitis (season 7), an autistic medical student who idolizes Shaun and was inspired to become a surgeon by the video of Shaun saving a young boy in the series premiere. While she isn't a savant like Shaun, she can hyperfocus. She seems to have a special interest in Taylor Swift. In a flashforward in the series finale, Charlie has become an attending at the hospital.
Wavyy Jonez as Dominick 'Dom' Hubank (season 7), a medical student who is squeamish around blood. In a flashforward in the series finale, Dom has opened his own clinic and is no longer has a fear of blood.
Bess Armstrong as Eileen Lim (season 7), Audrey's mother
Ruby Kelley as Hannah (season 7), a patient with a drug addiction who bonds with Dr. Glassman as Hannah reminds Glassman of his deceased daughter Maddie. Ruby Kelley is the daughter of Richard Schiff and Sheila Kelley who play Dr. Glassman and his former wife Debbie.
