The hospital struggles against the COVID-19 pandemic and forces changes on the way everyone lives: Shaun and Lea are obliged to remain apart, Park is staying with Shaun, Glassman works from home, and Andrews sleeps in his garage to protect his wife. The situation takes its toll on everyone: Shaun struggles with being so far from Lea, Glassman becomes overprotective of Debbie to the point of annoyance, and Lim and Claire become short-tempered. The episode primarily focuses on three COVID patients: a woman who doesn't survive whose daughter Claire empathizes with, a man who is in constant video contact with his wife and is put on a ventilator by Shaun and Andrews, and finally a pregnant woman with whom Park bonds and who he takes care of personally. Morgan treats a man with symptoms of diverticulitis, but later discovers that he has COVID and both she and nurse Deena Petringa have been exposed. While looking at the personal belongings of the hospital's COVID patients, Claire hallucinates Melendez.

Claire deals with her grief by returning patients' belongings to their families while hallucinating Melendez. Claire tracks down the owner of a set of dog tags left behind by a deceased patient and, with the encouragement of Melendez, decides to begin moving on with her life. At the same time, Lim struggles with the increasing losses of patients to COVID-19, Park continues to treat his formerly pregnant patient, and Shaun and Andrews attempt to save a man who must have his right foot and ankle amputated. Now working as an internist and recovered from her own bout with COVID, Morgan treats Nurse Deena Petringa whose condition continually worsens; the two women bond, with Deena offering Morgan advice based on her forty years of nursing experience. Deena ultimately dies of the virus, but Shaun's, Andrews', and Park's patients survive with one released three weeks later. Glassman opens up to and reconciles with Debbie while Shaun allows Lea to spend time with him in person again, Andrews decides to be with his wife instead of continuing to sleep in the garage, and Park decides to end his romantic relationship with Mia and continue co-parenting Kellan together instead.

Shaun, Claire, and Park are assigned to supervise six resident applicants with only four positions available while Morgan struggles with the transition to internal medicine. Andrews, Shaun, and Park treat a seventeen year old getting breast implants to fix a deformity; while the surgery is initially successful, she experiences complications that put her into a coma. It is determined that the patient formed a blood clot in her brain, but Andrews manages to remove it using a stent retriever. Morgan discovers that her patient has a tumor on his heart and enlists Claire and Lim's help to fix it, but has trouble stepping back from the case to the point that Lim has to throw Morgan out of the operating room; despite some difficulties, the surgery is a success and Morgan gives Claire credit as the surgeon responsible. While having lunch with Lea, Shaun inadvertently insults her but, after getting advice from Glassman, makes up with her by being totally honest about everything that he loves about Lea. The team selects doctors Jordan Allen, Asher Wolke, Olivia Jackson, and Enrique Guerin as the new residents; Lim reveals that Shaun, Claire, and Park will be helping to train the new residents and warns them not to take the responsibility lightly.

During a heatwave, Shaun and Danni work on a case together, but Shaun struggles to work with her after finding out she advised Lim not to do the surgery that he proposed. Danni keeps contradicting him during their work and he shoots down her ideas. After their recent arguing, Shaun removes her from the case but, after his patient wants Danni back on and Glassman advises him to find common ground with her, he and Powell resolve their issues and they save the patient. The rest of the staff treat elderly patients when the hospital has a blackout during the heatwave, losing some but saving many. Lea and Glassman work together to restore the power. Danni brings Lim to a disability basketball game, which helps her connect with people who share her condition.