The film begins with an introductory sequence involving the main characters and images from space. These virtually still images reveal the key elements of the film: Justine the bride in deep melancholy with birds falling behind her; of a lawn with trees and sundial with two different shadows; Pieter Brueghel's The Hunters in the Snow burning; the black horse collapsing in slow motion; Justine as a bride being swept along by a river; her wedding dress tangled in plant matter; and finally Justine and her nephew building their magic cave before Melancholia crashes into Earth.

Part One: "Justine"

Delayed by their stretch limousine's difficulty traversing the narrow winding rural road, newlyweds Justine and Michael arrive two hours late for their own wedding reception at the estate of Justine's sister, Claire, and her husband, John. Justine has a dysfunctional family: brother-in-law John appears to resent having to pay for the wedding; father Dexter is hedonistic and selfish to the point of narcissism, while mother Gaby is brutally jaded, her outspokenness leading John to throw her out of the house. No one ever asks what Justine wants, or why she is unhappy, but throughout the dinner she is praised for being beautiful. Claire urges Justine to hide her debilitating melancholy from her new husband Michael. Justine flees the wedding reception in a golf cart. Frustrated by excessive fabric, she tears her dress getting out of the cart. At the eighteenth hole of the golf course on the estate, she looks up at the night sky, squatting to urinate on the hole.

Justine's boss, Jack, is ruthless, greedy, and gluttonous. During his wedding speech, he's hustling Justine to meet a work deadline (she writes copy). He pushes her throughout the evening to create a tagline to promote a campaign based on a modern facsimile of Bruegel's The Land of Cockaigne (the mythical land of excess). She later opens an art book at this painting. During the cutting of the wedding cake, Justine and Gaby independently escape to take baths.

Justine's boss's nephew, Tim, is given the chance to exploit the opportunity to get the tagline at all costs in order to promote his career: a task similar to what Justine was previously so successful at. He reluctantly, but doggedly, pursues Justine throughout the wedding reception. She cannot consummate her marriage with her husband and eventually goes out onto a sand trap and has sex with Tim. Unable to get the tagline from Justine, Tim is later fired for his "professional" failure, but Justine also resigns, telling Jack that he is a "despicable, power-hungry little man." After several hours of being alienated from each other, Justine and Michael quietly agree to call off the marriage. Michael departs. Early the following morning, while horseback riding with Claire, Justine notices Antares is no longer visible in the sky.

Part Two: "Claire"

Later, the reason for Antares's disappearance has become public knowledge: a newly discovered rogue planet called Melancholia, which entered the Solar System from behind the Sun, was blocking the star from view. The planet has now become visible in the sky as it approaches ever closer to Earth. John is excited about the "fly-by" predicted by scientists, while Claire is frightened by alternate predictions of the earth being hit.

In the meantime, Justine's depression has grown worse. She is placed in the care of Claire and John. Justine is essentially catatonic and Claire is unable to help her, even to assist her into the bath. In an effort to cheer her up, Claire makes meatloaf. Justine admits that she is so numb that even her favourite meal tastes of ash.

As Justine is forced into waking patterns, her connection to her beloved black horse Abraham becomes remote and frustrating. On two occasions, the horse refuses to cross a bridge over a river. Justine acts brutally towards the horse and eventually whips him mercilessly to the ground.

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