Nic and Conrad contemplate their past when they team up to diagnose a happy husband and wife who are both admitted to the hospital with mysterious symptoms. Bell and Marshall butt heads on a work trip when their cut-throat business tactics don't align. Meanwhile, AJ turns down a request from Bell despite Mina's forewarning, Devon continues to gravitate to medical device rep Julian and the staff gears up for Conrad's three-year anniversary at Chastain.

When the hospital has a severe blood shortage, Conrad must try every avenue to save a patient's life. Nic receives devastating news and is left worrying about her sister's health, while Mina and Devon work with a new anesthesiologist who is not what she seems. Elsewhere, Kit considers the future of her intertwining relationships and Bell has an encounter with a woman from his past.

When a police officer brings in an injured criminal, the staff must keep him alive. Nic gets roped into a surgical rotation with Cain that leaves her questioning the way he operates. Conrad makes a shocking discovery about the hospital.

While looking for a distraction on Halloween, Conrad treats a group of witches who send the ER into chaos. Also, Devon treats a patient who thinks he is being haunted by ghosts. Meanwhile, on the way back from his vacation, Bell picks up a hitchhiker who is not what he seems to be.

When one of the doctors is shot outside the hospital, the ER is put into lockdown and the team races to save one of their own. Elsewhere, Devon and The Raptor work with a patient who learns he is unable to receive a lung transplant, due to his vaccination status. Meanwhile, Devon and Leela try to juggle the new dynamics of their relationship and Cade's father arrives at Chastain.

The high stakes governor election results in violence at the polls, causing multiple victims to arrive at Chastain. Conrad finds common ground with an aggressive patient, helping lead to a diagnosis for his outbursts. Meanwhile, when another patient’s lung collapses, the doctors find a serious root of the issue.

A famous cardiothoracic surgeon – who happens to be Dr. Yamada’s mentor – comes into Chastain after experiencing heart pain. Meanwhile, Kit breaks the news that the ER will no longer be accepting trauma patients due to budget cuts, and Devon and Conrad help treat a confused woman.