In 1862, Elizabeth "Lib" Wright (Florence Pugh), an English nurse who served in the Crimean War, is sent to a rural village in Ireland where she is tasked with closely watching Anna O'Donnell (Kíla Lord Cassidy), a fasting girl who according to her family has not eaten for four months. She stays at a local tavern run by Sean (David Wilmot) and Maggie Ryan (Ruth Bradley). The committee (headed by John Flynn (Brían F. O'Byrne), local doctor Dr McBrearty (Toby Jones) & Sir Otway (Dermot Crowley)) gives her 2 weeks to observe and report her findings. Anna is not to be fed forcefully, neither refused food if she asks for it.She is to be assisted by a nun, Sister Michael (Josie Walker), and the two are to report their findings independently to a council of local dignitaries. The trauma of the Great Famine still looms over the community (and the Irish blames the English for it), and many locals are wary of the English nurse. Lib meets Anna's deeply religious family: her mother Rosaleen (Elaine Cassidy), her father Malachy (Caolán Byrne) and her elder sister Kitty (Niamh Algar). At dinner, Lib learns that Anna's elder brother died of an unknown illness. Anna herself appears in good health and says she has been kept alive by consuming "manna from Heaven". Lib suggests shifting Anna to the hospital, but Rosaleen refuses.Lib, still grieving for the death of her only child, takes laudanum to help her sleep. She is widowed, and was married to her husband for only a year. At her lodgings, Lib encounters William Byrne (Tom Burke), a man who grew up locally and whose family perished in the Great Famine while he was away at boarding school. Now a journalist for the Daily Telegraph, William is reporting on the story, which he believes to be a hoax. Lib and William become intimately involved. Lib's observations initially reveal no evidence of deception. Anna prays many times a day and speaks of the fate of the damned in Hell.Noticing that her mother kisses Anna goodnight on her mouth while cupping her face, Lib deduces that chewed food is being covertly passed to Anna. She forbids the family from touching her. William says that by doing this Lib has condemned Anna to death as her family cannot confess the truth. If they confess, they will be driven from their home and tried for fraud. Anna does not deny that this is her "manna" (She says it was a holy secret, and the chewed up food was delivered to her by God, via her mother), and she discloses to Lib the reasons for her fast: her elder brother had repeatedly sexually assaulted her, and she attributes his death to God's wrath. Anna believes that by sacrificing her life she will free her brother's soul from the ceaseless burning in hell. Separated from her family's touch, Anna's condition worsens. Lib begs Dr McBearty to stop the watch and force Anna to eat. Dr McBearty speculates that maybe Anna has developed some capacity to convert sunlight into energy. William files a report to his paper in which he lays the blame for Anna's expected death on her family and the community.Lib informs the council of her findings (That Anna was being fed by her mother), but they refuse to believe her. Sister Michael states that she had found no evidence of Rosaleen feeding Anna. Members of the council question Anna, but she repeats that she is sustained solely by "manna from Heaven". Knowing that Anna will inevitably die unless she eats soon, Lib pleads for the family to take action, or at least for her mother to resume the kisses. Rosaleen refuses, saying that after Anna's sacred death, both her children will be in heaven. Lib persuades William to assist with a rescue plan. While the family are at mass, Lib brings Anna, now near death, to a nearby holy Clootie well. She tells her that although "Anna" will die, she will be reborn as a new girl named "Nan". Anna closes her eyes and appears to die. When she revives, Lib is finally able to feed her. Lib returns to the house alone and sets it ablaze, at the same time deliberately destroying her laudanum bottle.Lib tells the council that Anna died of natural causes, and that the fire was an accident. The committee is distraught since Anna would have been their first saint since the dark ages. Concerned for their own possible culpability for Anna's death, and in the absence of a body within the charred remains of the house, they terminate her employment without pay. Sister Michael tells Lib that, after leaving mass early, she saw a vision of Anna and an angel leaving the area on horseback. She asks Lib to swear that Anna has gone to a better place.In Dublin, Lib reunites with William and Nan, who has recovered her health. The three pose as a family named Cheshire and set sail for Sydney.