Dr. John Watson resumes his medical career as the head of a clinic dedicated to treating rare disorders six months after the passing of his friend and partner, Sherlock Holmes, at the hands of Moriarty.

Watson and the fellows investigate the perplexing case of a family man with a bullet lodged in his head who insists he is a Scottish soldier and seems to be hiding something nefarious. Meanwhile, Watson looks for clues to whom his estranged wife Mary is dating, and Ingrid tries to work out what her "tell" is when Watson calls her out for lying.

Watson and the fellows treat a comedian who collapses at an open mic night and seeks their help, but throughout the investigation her past is revealed to be much more complex than initially believed. Meanwhile, the team becomes concerned when Watson himself collapses and suffers another traumatic brain injury as he continues to hide his worsening symptoms.

When Sasha discovers a link between her current patient, who has advanced cancers and distinctive lesions on his tongue indicative of Cowden syndrome, and a cadaver she dissected during medical school, the team traces the case to Amish country.

Watson takes a major ethical risk when he decides to treat a sickle cell patient with an unorthodox surgery, and the team faces their own dilemma when they must decide whether to look the other way or help the young woman. Meanwhile, Ingrid struggles to get her sister admitted to her spinal project.

Stephens musters the courage to ask Watson to help him when his camgirl suddenly collapses during a video call. He does not know anything about her real life, so the team must act quickly to locate her before it's too late. Meanwhile, Watson grapples with guilt over Sherlock's passing and Sasha has doubts about her relationship.

While Watson and the team help a woman whose memory resets every three minutes, Watson struggles with auditory hallucinations and questions whether someone is behind his current decline. Meanwhile, Moriarty plans his next move.

Watson runs into brilliant con artist and an old friend of Sherlock Holmes, Irene Adler, when her son Angus is admitted to UHOP for temporary paralysis. The fellows help Watson after he grows fond of Angus and pursue various leads to find a cure to his illness.

Ingrid's lies come back to haunt her when her sister Gigi needs to be treated by the team after she develops side effects to the secret treatments Ingrid put her through. Also, Watson and Mary bond over a tragedy.

Watson must confront the dark side of medicine when a patient is accused of cuddle.

Watson confronts a traumatic event from his Army days that still weighs heavily on him when his Army veteran friend's wife reaches out begging for help when her husband is seemingly having a psychotic break. Meanwhile, Shinwell is asked for one last favor by Moriarty.

When part of the team falls ill after becoming targets of a sinister plot, it becomes an all-hands-on-deck situation to save them before it's too late.

Watson announces a new ambitious project that he has been working on.