Anderson employs the first person point of view. The fourteen-year-old protagonist, Mattie, gives readers the facts of Philadelphia and the epidemic quickly.

Anderson selected the title Fever 1793 because the story occurs during the period when Philadelphia suffered severe losses from the 1793 yellow fever epidemic. Set in the post-Revolutionary era, the story explores the worldwide themes of friendship and death. As Mattie matures, she learns perseverance, hope, and self-reliance.

Mattie is in conflict with her mother, at odds with her body, and is dreaming about her future when she hears about the death of her childhood friend Polly. Shocked, she finds little time to grieve as she helps her mother serve coffeehouse clients. Confused about what killed Polly, Mattie and her family begin to hear about yellow fever but quickly dismiss the predictions as pessimistic.

Readers learn in the first chapter about Mattie's crush on Nathaniel Benson. Nathaniel enjoys Mattie's sharp wit and her zest to try new things. Together they reminisce about the launch of Blanchard's hot air balloon, an event symbolic of the new attitudes that Mattie and Nathaniel embrace. Nathaniel gives Mattie flowers as a way to remember him as the city locks its doors to the fever. Mattie's memories help her to endure her many hardships. It is this hope that keeps Mattie going until the first frost that ends the epidemic.

Lucinda, Mattie's mother, serves as the antagonist. Widowed for several years, she raises Mattie by herself as she manages the coffeehouse. Lucinda knows how to persevere through tough times, and she passes on this ability to Mattie.

Mattie describes her mother as the type of person who "had given birth . . . in the morning and cooked supper for ten that night." Lucinda drives herself hard. Luanda's callous character forces Mattie to stand up for herself. Mattie wonders if her mother enjoys her life or if it is filled with bitterness. She shows little compassion for herself or for Mattie, making Mattie's journey to adulthood a hard one.

Lucinda gets yellow fever. Mattie finds out when a stranger dumps her out of a wheelbarrow in front of the coffeehouse. For the first time, Mattie sees her mother out of control. Mattie fears for her mother's life as she sees her mother shiver and vomit uncontrollably. Luanda's eyes are poisoned with streaks of yellow and red. Mattie, like her mother, puts her fears and sadness aside so that she can go about the business of taking care of her mother.

Fearful that Mattie will catch the contagious disease, Lucinda sends her out of town to the Ludingtons at Gwynedd with Mattie's grandfather. Mattie experiences a mix of emotions. She wants to nurse her mother to health and ensure she is okay, yet she feels helpless against this unknown and deadly virus.

Mattie does not find out if her mother survives the fever. This unresolved conflict effectively adds to the suspense of the novel.

Mattie's grandfather, Captain William Farnsworth Cook, protects her like a father figure. He teaches her practical lessons. For example, he frequently interrogates her about what a soldier needs to fight. Mattie answers: a sturdy pair of boots, a full belly, and a good night's sleep.

Mattie and her grandfather leave for the Ludingtons. Grandfather's cough and drowsiness raises their coachman's suspicions about his health. Fearing the grandfather has yellow fever, the coachman dumps Mattie and Grandfather outside Pembroke.

Mattie cares for her grandfather. She makes good decisions that provide them with shelter, food, and water. This experience cultivates her self-confidence and she experiences self-reliance.

Grandfather and Mattie travel together, overcoming several misfortunes. Grandfather takes Mattie to Philadelphia when she catches yellow fever. He helps nurse her back to health, and they return to the abandoned coffeehouse. Grandfather dies in a battle against thieves who have come in the middle of the night to ransack the coffeehouse.

Mattie grieves his death and remembers his life. She demands a reading from the Bible at his burial in a mass grave as a way of honoring him. Mattie's relationship with her grandfather enables her to expand her self-reliance and perseverance. It teaches her practical ways to handle tough situations, and it provides her with courage to win her battles.

After Grandfather's death, Mattie reaches her lowest point. The life she knew has vanished. The coffeehouse is vandalized and empty. Disease and death surround her. Mattie wanders the streets, wondering what to do.

She discovers baby Nell cowering in a corner and sucking her thumb, her blonde hair loose and tangled, her feet bare and black with dirt. Nell's mother has died of the fever. Mattie decides to care for Nell.

She finds Eliza, Lucinda's valued peer, who joined the Free African Society. Thick into the action, Eliza befriends Mattie. She asks Mattie to work alongside her as an equal, thus giving Mattie the opportunity to further realize her self-worth. She does not interfere when Mattie makes her own decisions, helping Mattie mature to the woman she is quickly becoming.

When Nell contracts yellow fever, Mattie and Eliza follow the French medical treatment: fresh air, rest, and fluids. Her suggestion works, and Nell heals. Nell symbolizes hope for a brighter future, and she enables Mattie to take on the responsibility of adulthood.

At the novel's resolution, Mattie's character transforms as she realizes that she must persevere. She knows that she has many choices. Mattie cultivates her friendship with Nathaniel. She opens up the coffeehouse with Eliza as her partner and begins to implement her dreams for a growing business. Nell stays with her and depends on her like a mother.

Lucinda returns from the country in ill health. Forced into a life of leisure, Lucinda must also depend on and trust in Mattie to run the coffeehouse. Lucinda begins to respect Mattie's choices and to treat her with respect and compassion.

Anderson does an excellent job of developing believable characters with realistic themes set against a rich background. She shows how this disease changed her characters, much as horrific life events change real lives. Young adults will emerge from this novel with a sense of hope, perseverance, and understanding.