The start of Severance introduces readers to Candace Chen, the main character and protagonist of the novel. At the start of the novel, Ma lets readers know that society has collapsed as a result of the Shen Fever, a disease (turned pandemic) that makes those infected with it repeat routines without thought until they eventually die.
The novel also features flashbacks of Chen's life. Chen and her parents immigrated from China to Salt Lake City, Utah in her youth as her parents sought a better life for everyone. But Chen doesn't stay in Salt Lake City for very long. In fact, she went to New York City after her parents’ death (her parents left her a sizeable inheritance which she used to drift through life). Eventually, running out of money and being exceptionally unfulfilled, Chen decides to take a job at a company that produces high-quality versions of the Bible with unique design variations.
In another flashback, Chen discovers that she is pregnant with her boyfriend Jonathan's baby (the two broke up just before Chen found out the news). But the aforementioned pandemic, which had long been looming in the United States, is quickly growing out of control. Businesses have begun to shut down, but Chen's company pays her to stay in the office to make themselves look good. After all, no reputable company closes down in the face of a pandemic. With no family in the same country as her, Chen doesn't want to leave New York City as most people do, so she stays. Eventually, as her colleagues succumb to the disease, she is the only person left in the office. And eventually, her entire company.
At the suggestion of her ex-boyfriend, Chen decides to take up her old hobby once again and begins to take photos of the deserted New York City, something which she posts about in a blog. Eventually, Chen discovers that she has fulfilled her contract and is one of the last people to escape New York City.
In the present day, Chen — who readers discover is immune from the disease — is near death on a highway in Pennsylvania. She is found by a group of survivors — other immune people — taking Chen to their facility, where they promise she will be safe. But their group is more complex than they initially seem. They have religious tendencies and are ruled by a dictatorial figure named Bob, who encourages the group to raid houses and murder the "fevered" (or those infected with the Shen Fever).
But a member of the group, who they had initially thought was immune, succumbs to the disease after visiting their family house. Chen posits the group member was able to succumb to the disease because she had overwhelming feelings of nostalgia.
Eventually, the group makes it to their new home in Illinois. Bob, however, still doesn't know that Chen is pregnant. And when he does find out, he has her imprisoned for her disloyalty. Chen eventually determines, with the help of her dead mother, who comes to her in hallucinations, that she is only safe from Bob until her baby comes. She thus hatches a plan to escape, which she successfully does, heading to Chicago in Bob's stolen car.
