The film opens with a sickly man, Bud (David Pendleton), wheezing and covered in boils. His daughter Sarah (Carmen Ejogo) gently talks to him wearing a gas mask, assuring him things will be okay. Afterwards, Carmen's husband Paul (Joel Edgerton) and their son Travis (Kelvin Harrison, Jr.) wheel Bud into the woods. Travis places a pillow over his grandfather's head and shoots him. Bud's body is dumped into an open grave, doused with lighter fluid, and set on fire.
The family lives together with their dog Stanley, kept away from the rest of the world as it is implied that a fatal virus has devastated most of the country, and nobody knows what is really going on out there.
Travis frequently experiences nightmares. He sees himself walking into a room in the house and seeing a sick, wheezing man on the bed. As Travis approaches him, the man shrieks. Travis wakes up, and his parents realize someone is trying to break into the house. A loud banging is heard at the door. Paul and Sarah grab their guns and head to the front. Paul gets ready as the assailant tries breaking the door open. He gets the door open, and Paul shoots at him but misses. It is a man named Will (Christopher Abbott). Paul orders him to drop his gun and get on the floor. He questions Will to know if there are other people outside. Will says no, and Paul knocks him out with the butt of his gun.
Paul ties Will to a tree outside and puts a large sack over his head with tape on his mouth, leaving him yelling. This gives Travis another nightmare where he sees Will looking over at him with darkened eyes.
After about a day, Paul carefully approaches Will by the tree and he takes the sack off. Paul offers Will water if he gives him honest answers, and he shows Will his gun in case he tries to pull anything. Will explains that he thought Paul's house was abandoned, and he only tried looking for water, food, or any supplies he could gather for his wife and child, who are several miles away. He claims to have seen nothing and nobody for 80 miles. Will also offers Paul some goats and chickens for food in exchange for help. Believing Will, Paul lets him have some water.
Paul drives Will in a pickup to go look for his wife and child. While passing through the woods, Paul's truck is shot at. He grabs his gun and gets out of the car. He sees one man approaching and he shoots him dead. Will is beating up another man, and Paul tells him to get off. Will tells Paul not to shoot the man, but he does. Paul then asks if Will knew the men, but Will didn't. He wanted to keep the man alive to get information as to what's going on out there.
The two return to the house with Will's wife Kim (Riley Keough) and their toddler son Andrew (Griffin Robert Faulkner). Paul and Sarah welcome the family into their home but lay down some rules so there won't be any problems.
Both families carry on about their normal lives. They spend some time together eating or playing board games. Will and Kim frequently get intimate. Travis develops a crush on Kim and is seen listening in on her and Will's conversations. He has a dream where Kim walks into his room in her underwear. She mounts and kisses Travis, only to start spewing black bile into mouth.
Travis goes into the kitchen and finds Kim sitting there by herself. He startles her at first but they sit to have a conversation since they can't sleep. Kim mentions wishing she could have sweet foods but Travis says he doesn't like cupcakes or cookies or anything like that, which she finds to be sad.
The next night, Stanley starts barking at something. The men go outside and try to find what is bothering the dog. Stanley runs further into the woods, still barking at something, with Travis chasing after him. Stanley eventually stops barking and disappears from sight. Paul scolds Travis for going off by himself.
Later on, Travis finds Andrew in the living room lying on the floor. Andrew doesn't remember getting there. Travis takes the boy's hand and brings him back to his room. Suddenly, a thumping sound is heard in the house. Travis runs to tell his parents. Paul and Sarah grab their guns. Everyone looks in the kitchen and finds Stanley bleeding and weak. Knowing he is sick, Sarah takes Travis away while Paul mercy-kills Stanley. Travis hears the gunshot and starts crying. Paul burns Stanley's body too.
Everyone sits down to discuss what has happened. Travis explains that he found Andrew and saw that the door between the kitchen and living room had already been opened before Stanley was found. Will and Kim get defensive when Travis asks if Andrew sleepwalks. When asked, Andrew says he doesn't remember getting out of bed. Paul then suggests that both families should just not interact with each other for a while. Paul later asks Travis about Andrew, and asks if he touched the boy. Travis says he only took his hand to guide him upstairs, but Paul is upset that Travis didn't use gloves, believing that the other family may be carrying the virus.
Travis has another nightmare in which he is sick and covered in boils. He spits up bile and sees Bud sitting on the bed across from him, wheezing and with completely black eyes.
In the morning, Andrew is heard coughing and whining. Paul knocks on Will and Kim's bedroom door to ask to come in and take a look at Andrew, with Sarah armed in the corner. When Will doesn't answer, Paul demands that he open the door or else he will break it down. Will complies but then takes Paul's gun and turns it on him, making him go inside. Holding Paul at gunpoint, Will says he only wants to get whatever supplies he can take and leave with Kim and Andrew. He threatens Paul if he goes near his family. Will takes Paul outside at gunpoint, and Sarah has hers aimed at Will. They agree to lower their guns, but Paul hits Will and takes his.
Paul wheels Will away into the woods while Sarah has Kim at gunpoint. After Paul dumps Will, Will gets up and starts attacking Paul. He bashes Paul's head with a rock until Sarah shoots Will. Kim runs away with Andrew. Paul aims his gun at Kim and shoots. He ends up killing Andrew first. Kim screams in despair and yells at Paul to shoot her, which he does. Will slowly dies. Travis runs into the scene. Sarah notices Travis looks unwell. He drips fluid from his nose and he runs to the bathroom to throw up.
After sometime, Travis is almost completely consumed by the virus. Sarah sits over him in the bed, trying to assure him things will be okay. We then see Travis walking through the corridor in his house with a lamp before going over to the window. Sarah tearfully tells Travis he can let go now. Paul is in the other room alone, weeping.
The last shot is of Paul and Sarah sitting at the table in silence.
*CUT TO THE CHASE*
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A deadly virus has taken over the country. A man named Paul has been doing everything he can to protect his wife Sarah and son Travis from whatever is out there. Their life is disrupted when another man named Will shows up trying to break into the house for supplies. After learning Will means no harm, Paul allows him and his wife Kim and son Andrew to stay with them.
After an encounter with two attacking strangers in the woods and Paul's dog coming home infected, Paul begins to distrust Will and his family, thinking they may be carrying a sickness with them.
Will tries to leave with enough supplies for himself and his family, but things escalate when Will tries to attack Paul. Sarah shoots Will and Paul kills Kim and Andrew. Unfortunately, Travis becomes infected and he dies, leaving Paul and Sarah alone in their sorrow.
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