Eel is a thirteen-year-old orphan who works as a "mudlark" scavenging the filthy banks of the River Thames, while also running errands for the Lion Brewery. He keeps his real name and his younger brother's whereabouts a strict secret to protect them both from his abusive stepfather. Clever, industrious, and literate, Eel desperately attempts to earn enough pennies to pay for his brother's boardinghouse rent.

Florrie is a twelve-year-old girl who works as a scullery maid but harbors quiet ambitions of becoming an artist. She is deeply pragmatic about the hardships of their social class but remains fundamentally kind and optimistic. She readily volunteers her drawing skills to help Eel and Dr. Snow map the neighborhood to track the disease.

Dr. Snow is a privileged, upper-class physician and scientist who strongly disputes the prevailing "miasma theory" of disease. He believes the cholera outbreak is caused by contaminated water and sets out to prove his hypothesis using systematic interviews. Kind but highly focused, he acts as an educator to Eel, teaching him the scientific method.

Fisheye Bill Tyler is Eel's cruel, physically abusive stepfather. He operates as a street criminal and actively hunts for Eel in order to locate Henry, believing the younger boy's innocent looks will make him an excellent tool for begging and thievery.

Henry is Eel's younger brother, hidden away in a boardinghouse to keep him safe from their stepfather. He has a sweet, innocent appearance that makes him a target for exploitation in the criminal underworld. He attends school thanks to Eel's financial sacrifices.

Reverend Whitehead is the local junior curate in the Broad Street neighborhood. He works tirelessly to provide spiritual and emotional comfort to the suffering families. Though he initially believes the bad air causes the illness, his dedication to the community leads him to collaborate with Dr. Snow's investigation.

Thumbless Jake is an older mudlark who once threatened Eel but later helped him secure a steady job at the Lion Brewery. He operates by a rough street code, acting as both a rival for river scraps and an essential ally against more dangerous threats.

Nasty Ned is a malicious mudlark who frequently bullies Eel and claims segments of the river as his territory. His self-serving behavior makes him an unpredictable and dangerous presence on the riverbanks.

Mr. Griggs is a respected local tailor in the Golden Square neighborhood. He is a gentle man who thinks highly of Eel, prompting Eel to seek his help to prove his honesty against theft accusations.

Bernie is the five-year-old son of Mr. Griggs. He is deeply frightened and affected when the cholera epidemic strikes his family home.

Betsy is Mr. Griggs's seven-year-old daughter. She takes responsibility for her younger brother and the family dog, Dilly, when sudden illness disrupts their household.

Mrs. Miggle is a stern landlady who runs the boardinghouse where little Henry lives. She demands punctual payment, forcing Eel to take on dangerous and exhausting jobs to ensure his brother is not turned out onto the streets.

Abel Cooper is the foreman at the Lion Brewery where Eel is employed. He appreciates Eel's speedy messenger work and shares the common public belief that invisible miasmas cause illness.

Mr. John is one of the owners of the Lion Brewery. He hastily believes his nephew's lies over Eel's word, threatening Eel's livelihood and shelter without conducting a proper investigation.

Hugzie is the lazy and dishonest nephew of the Lion Brewery owners. He steals money from the business and blames the missing funds on Eel, leveraging his class and family connections to avoid consequences.

Mr. Edward is the other owner of the Lion Brewery. Unlike his brother, he is observant and fair-minded, eventually recognizing Eel's hard work in the community during the epidemic.

Mrs. Weatherburn is Dr. Snow's fiercely loyal and highly protective housekeeper. She maintains a strict watch over the doctor's Sackville Street household and is initially highly suspicious of Eel's presence.

Mrs. Lewis is a resident of Golden Square. Her household routines and use of the neighborhood water pump become central to understanding the timeline and spread of the cholera outbreak.

Fanny is the infant daughter of Mrs. Lewis. Her early illness plays a crucial role in Dr. Snow's investigation into how the cholera epidemic began.

Annie (also known as Ribbon Annie) is the older daughter of Mrs. Lewis. She helps her mother run the household during the severe stress of her infant sister's illness.

Charlie is a worker tasked with hauling away the bodies of those struck down by cholera. Unlike some in his grim profession, he treats the deceased with respect and offers Eel temporary, grueling employment during the crisis.

Dr. Farr works at the office that keeps records of births and deaths in London. He assists Dr. Snow by providing access to the mortality data needed to map the epidemic, even though he remains skeptical of the water-borne theory.

Kate is a criminal associate of Fisheye Bill Tyler. She assists in his violent schemes and helps restrain Eel during interrogations, showing no sympathy for the boy's suffering.

Dilly is the beloved dog belonging to the Griggs family. When the epidemic forces the surviving children to relocate without her, Eel takes responsibility for the animal.

Little Queenie is a small cat rescued from the river by Eel. She provides Eel with a small measure of comfort and companionship in his quarters at the Lion Brewery until the foreman takes a liking to her.

Danny is Florrie's brother. He helps care for his sister when she falls ill and provides Eel with updates regarding her condition while handing over the map she drew.

Gus is a Broad Street boy who works delivering water. His deliveries inadvertently help spread the contaminated water to neighborhoods farther away, providing a crucial clue for Eel's investigation.

Mrs. Eley is a widow living in Hampstead, far from the cholera outbreak. Because she prefers the taste of the Broad Street pump water and has it delivered, her case provides the evidence Dr. Snow needs to prove his theory.

Mrs. Flanders is Betsy Griggs's aunt. She steps in to care for her niece after tragedy strikes the Griggs family, though she initially refuses to take in the family dog.