Sofi is a resilient woman of Native and Spanish heritage living in Tome, New Mexico. At eighteen, she married a gambler named Domingo, who eventually abandoned the family for twenty years. As a single mother, she raises her four daughters, managing the family farm and working at a meat market. She is a practical, long-suffering, but determined matriarch who pushes back against the lazy men in her life.

Caridad is Sofi's second oldest daughter, whose name translates to "Charity." She drops out of college and marries her high school sweetheart, but his infidelity triggers a downward spiral of heavy drinking and casual encounters. After suffering a brutal attack that leaves her mangled on the side of the road, she undergoes a miraculous physical recovery. She subsequently displays clairvoyant abilities and a deep connection to spiritual healing, eventually becoming an apprentice curandera.

The youngest of Sofi's daughters, La Loca earns her nickname due to her peculiar behavior following a miraculous resurrection at age three. She claims to have visited heaven, hell, and purgatory while temporarily dead. She is intensely reclusive, deeply averse to physical touch, and spends her time by the ditch near her mother's home. She possesses uncanny premonitions and the ability to heal others.

Fe is Sofi's second youngest daughter, a bank teller who desperately wants a normal, highly ordered life. She focuses completely on her upcoming wedding to her fiancé, Tom. When Tom abruptly ends their relationship via letter, her structured world collapses. She suffers a massive psychological breakdown, spending an entire year doing nothing but screaming.

Esperanza is Sofi's eldest daughter and the most independent of the siblings. She earns a bachelor's degree in Chicano Studies and a master's in Communications, eventually working as a television journalist. Despite her professional drive, she is continually pulled back to her college boyfriend, Rubén. She compromises her own advancement for a man who treats her poorly.

Domingo is Sofi's husband, who charmed her when she was fourteen with his good looks and bold attitude. He is a charismatic but irresponsible man with a severe gambling problem. Sofi banished him from the farm shortly after La Loca's birth due to his habits. He mysteriously returns two decades later and comfortably resumes living at the farm without explaining his absence.

Doña Felicia is an elderly, respected curandera in the community. She speaks multiple languages and has survived significant personal tragedy, including the deaths of husbands and children. She acts as the landlady for the trailer park where Caridad moves. Recognizing Caridad's latent mystical abilities, she takes the young woman in as an apprentice to teach her traditional healing practices.

Francisco is doña Felicia's godson who came to live with her after his mother died. Following a traumatizing stint in the Vietnam War, he returned home listless and emotionally numb. To find purpose, he trains as a santero, carving wooden statues of saints. He later joins the penitentes, a lay Catholic brotherhood, but struggles with intense earthly desires that clash with his religious convictions.

Tom is Fe's fiancé. His sudden decision to break off their engagement shatters her perfectly planned life. His departure triggers Fe's severe, year-long psychological breakdown.

Rubén is Esperanza's old college boyfriend. They maintain an intermittent relationship centered around attending the Native-American Church and physical intimacy. He is emotionally unsupportive, yet holds enough sway over Esperanza that she sacrifices professional opportunities for him.

Memo is Caridad's first love and husband. His infidelity early in their marriage ruins their relationship. This betrayal catalyzes Caridad's downward spiral into drinking and casual affairs.

Casimiro, often called Casey, is Fe's cousin and later romantic interest. He works as an accountant but carries the quirks of his ancestors. He has a peculiar habit of bleating like a sheep, a nod to his family's long history of sheepherding.

Esmeralda is a beautiful Native Acoma woman. She works as an attendant at the Ojo Caliente mineral baths. She instantly captivates Caridad during a religious procession, awakening a deep affection in the recovering clairvoyant.

Maria is a tarot card reader and social worker returning to her ancestral homeland of Truchas, New Mexico. She and her partner Helena experience a harrowing encounter with an aggressive local driver on their road trip. This event highlights the cultural and gender-based hostilities in the region.

Helena is a landscaper and Maria's partner. While driving on the roads of New Mexico, she faces down a hostile local man in a pickup truck. She actively protects them when he attempts to run their car off the road.

Dr. Tolentino is a local physician who blends Western medical education with spiritual practices. He performs "psychic surgery" and operates alongside traditional curanderas. He views science and faith as complementary rather than opposed.

Pedro is Francisco's uncle. He trains the young man in the traditional art of the santero. By teaching him to carve wooden figures of saints, he helps guide Francisco out of his post-war depression.

La Llorona is a mythical weeping woman from folklore who wanders the earth searching for her lost children. In Tome, she manifests as a spiritual presence. She visits La Loca near the ditch to deliver news from the spirit world.