Dr. Murphy treats a patient who has an illness that is not only unpredictable in nature, but also unlike anything he or the team has seen before. Dr. Claire Brown continues to work through her grief, still reeling from Dr. Neil Melendez's death.

With several candidates vying for residency at St. Bonaventure, Chief of Surgery Dr. Audrey Lim tasks Dr. Shaun Murphy, Dr. Claire Browne and Dr. Alex Park with mentoring the top first-year resident contenders. As their mentees shadow them for the day, Shaun and Park meet with Andrews to discuss a difficult surgery scheduled for a minor. Later, Shaun inadvertently insults Lea while discussing the pros and cons of the controversial surgery. And elsewhere, Dr. Morgan Reznick seeks out Claire and Lim’s help on a consult.

Dr. Morgan Reznik and Dr. Shaun Murphy's pregnant patient with twins is having pain and they are forced to grapple with a decision no one wants to make. Meanwhile, Shaun asks Lea to move back in despite her reservations

Dr. Shaun Murphy questions his decision to give the new residents autonomy when one of his intern's misdiagnosis of a patient has dire consequences. Meanwhile, Dr. Claire Browne, Dr. Alex Park and Dr. Jordan Allen treat a patient with a ruptured cyst affecting key functions of her brain. And elsewhere, Dr. Morgan Reznick and Park bond over failed relationships.

As Chief of Surgery Dr. Audrey Lim struggles to cope with the residual emotional trauma of COVID-19, she encounters a young war veteran fighting debilitating PTSD. After discussing his case with the team, Dr. Claire Browne suggests a radical treatment to help him. Meanwhile, still reeling from the recent loss of his mentee’s patient, Dr. Shaun Murphy declares he doesn’t want to teach the new residents anymore. And elsewhere, an eccentric patient keeps the team entertained.

Dr. Morgan Reznick discovers her patient’s wealth and obsession with extending his life is a dangerous mix that could end up costing more than he can afford.

The team treats a teenage gymnast who experiences complications from her intensive training. Meanwhile, Shaun meets Lea's parents for the first time.

Lim is challenged by the unique circumstances surrounding a pregnant patient with an aggressive tumor. Elsewhere, after misdiagnosing a patient, Claire makes a disconcerting discovery about certain practices at the hospital.

When the hospital is hit with a cyberattack threatening to shut down life-saving machines, Lea rises to the challenge and looks to outsmart the hackers to prove herself. Meanwhile, the team treats an inspirational cancer survivor-turned-successful-philanthropist who harbors a dark secret.

After bringing in an incredibly unique and complicated spinal surgery, Dr. Aaron Glassman challenges the residents for an opportunity to join him in the operating room. Meanwhile, Shaun and Morgan disagree on how to treat a comatose patient with a cancerous tumor.

When a renowned surgeon comes to St. Bonaventure for treatment, the team’s enthusiasm is quickly overshadowed by the doctor’s behavior. After studying his case, Dr. Shaun Murphy sees a pattern he recognizes. Meanwhile, Shaun and Lea are forced to make a life-changing decision that will alter the course of their relationship.

Claire is blindsided when her absentee father shows up at her door. Meanwhile, Shaun feels disconnected from Lea, causing tension in their relationship.

After finding out the gender of their unborn child, Lea's enthusiasm prompts Shaun to make an effort to be a more supportive partner. Meanwhile, the team treats a navy pilot whose previous doctor's misdiagnosis compromises her chances at a full recovery.

After a political protest turns violent, the team races to save two young gunshot victims.

Shaun struggles with his role as Lea's partner after complications arise with the pregnancy and his instincts as a medical professional kick in. Meanwhile, Dr. Park, Dr. Andrews and Asher disagree on how to address an elderly patient's wishes.

Dr. Claire Brown and the team must face hard truths about what lines they are willing to cross when one of Claire's idols becomes her patient.

Shaun and Lea go on a camping trip to distract themselves from their grief over their miscarriage. Meanwhile, Morgan and Park argue about the best course of treatment for their patient.

The St. Bonaventure team travels to Guatemala on a surgical mission to help patients at a rural hospital. Once there, the team faces a small community that is in desperate need of their help but are assigned the daunting task of identifying who they can help most. And while Shaun seems to be thriving in Guatemala, Lea is still struggling with the loss of her baby.

Dr. Shaun Murphy must perform a risky surgery on a patient without electricity when the power suddenly goes out. Meanwhile Lim and Dr. Mateo Rendón Osma’s relationship deepens as they overcome difficulties during the surgery.