While stuck at a wedding in Palm Springs, Nyles (Andy Samberg) meets Sarah (Cristin Milioti), the maid of honor and family black sheep. After he rescues her from a disastrous toast, Sarah becomes drawn to Nyles and his offbeat nihilism. But when their impromptu tryst is thwarted by a surreal interruption, Sarah must join Nyles in embracing the idea that nothing really matters, and they begin wreaking spirited havoc on the wedding celebration.

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A loner and cook (John Magaro) has traveled west and joined a group of fur trappers in Oregon Territory, though he only finds connection with a Chinese immigrant (Orion Lee). The men collaborate on a business, although its longevity is reliant upon the participation of a wealthy landowner's prized milking cow.

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