Dr. Shaun Murphy and Dr. Alex Park treat two patients who collapse at the local airport and whose symptoms point to an infection that may become airborne. The staff races to contain the infection before it spreads to the rest of the patients in the ER, resulting in a hospital quarantine during the holidays.

The hospital is still in quarantine as Dr. Shaun Murphy continues to be overwhelmed by the chaos and noise in the emergency room; Dr. Morgan Reznick struggles to keep her patients alive, and Dr. Audrey Lim fights for her life. Meanwhile, Dr. Neil Melendez and Dr. Claire Browne must find a way to complete their patient’s bone marrow transplant, despite the quarantine.

Dr. Andrews tries to convince a grieving family to donate their teenage daughter’s face to another young girl whose face was horribly disfigured in an accident.

Shaun’s blunt honesty with a distraught mother of a critically ill newborn baby causes the new chief of Surgery to question keeping him on as a resident.

The new chief of surgery, Dr. Jackson Han, believes Dr. Shaun Murphy is a liability more than an asset and works to keep him out of the operating room permanently.

As a barroom fight sends Dr. Shaun Murphy to seek treatment at St. Bonaventure’s, Dr. Alex Park and Dr. Audrey Lim disagree over an elderly woman’s post-operative symptoms. Meanwhile, Dr. Neil Melendez and Dr. Lim make their romance public, and Dr. Aaron Glassman continues to pursue a relationship with a good friend.

Dr. Shaun Murphy proposes a radical surgery to save a woman's life after what he believes was a disastrous first date with Carly. Meanwhile, after the new chief of surgery, Dr. Audrey Lim, announces that the residents can lead surgeries, Dr. Morgan Reznick and Dr. Alex Park compete for the chance to operate on an elderly patient who has been diagnosed with cancer.

Dr. Claire Brown faces complications at home and work as she prepares to lead her first surgery. Meanwhile, a sports fishing accident challenges the rest of the staff as they look to treat the fisherman’s injuries without damaging his prize catch.

Carly’s attempts at increasing her intimacy with Shaun are becoming more of a frustration than either of them expected. Meanwhile, Lim and Melendez struggle in their relationship as they work to separate their work from their personal life.

The city of San Jose is rocked by a massive earthquake that puts the staff of St. Bonaventure Hospital on high alert as they race to assess the damage and account for the safety of their colleagues and friends. Meanwhile, Dr. Neil Melendez and Dr. Aaron Glassman are attending a charity event when their lives are threatened by the earthquake.

The staff of St. Bonaventure Hospital works against time and their own personal safety to save the lives of those around them.

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.

Shaun has a hard time balancing his fears and concerns about potentially jeopardizing Lea's health and wanting to be with the woman he loves. Claire looks for a way to grieve Melendez's death. Park and Mia discuss their future together.