O vôo 815 da companhia aérea Oceanic Airlines, cai na costa do que aparenta ser uma ilha tropical deserta, forçando o grupo de estranhos a trabalhar em conjunto para se manterem vivos. No entanto, a sua sobrevivência é ameaçada por vários mistérios, incluindo uma escotilha metálica enterrada no solo, uma criatura que vagueia pela selva e os habitantes da ilha conhecidos como "Os Outros". Os sobreviventes descobrem que um dos seus não é quem parece ser e encontram uma mulher francesa chamada Danielle Rousseau, cuja equipe naufragou há 16 anos.
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