The film starts with three friends playing football during a storm. One of the friends, Jacob, is shot with a dart by a mysterious shooter. Because he was shot the moment lightning flashed, the other friends, Davis and Michael, assume Jacob was struck by lightning. The mysterious shooter runs over to Jacob, removes the dart, and pretends he is checking on Jacob. The friends take Jacob home and get him medicine while he is sleeping. When they wake him up, they find he is gone. Davis quickly finds him outside. Jacob is talking to an imaginary person, Ava, and can't see or hear Davis and Michael. During a dinner between Jacob and Ava, Michael slips him a note informing him of the situation. Jacob realizes he is insane and takes the medicine.Jacob is now better, but he is afraid of people, preferring to remain alone. While walking in the park, two people picnic near him, causing Jacob to hide. He trips and cuts his leg, but then wakes up in his bed. The next day, Davis is making dinner and asks Michael if he thinks Jacob remembers cutting his leg a few days ago, to which Michael replies that he probably wouldn't because he was asleep the whole time. Jacob, sick of being treated like a child, runs away. By the time Davis and Michael find him, he is unconscious in a pool of blood.The film flashes forward three months to the three friends, including Jacob, stealing donuts from an empty bakery. While driving home, they discuss life as the only humans left and trying to find their purpose in life. The film cuts to black as Michael screams, "What the hell is that?" The film flashes back three months to where it left off before the flash-forward.The three friends are watching the news, which informs them of a new deadly disease taking the world by storm. They are informed that any blood exposure within the last few months would guarantee they were exposed. Jacob is visibly distressed, remembering when he passed out in the pool of blood. Davis and Michael had thought he committed suicide, but a doctor reveals in a flashback that one of his stitches from the previous wound had simply burst open. Jacob is convinced he has the deadly disease, and after the cure is destroyed, the friends take him downtown to get his mind off of it. While at the restaurant downtown, the news breaks that one billion people had died from the disease. Jacob opens up about his imaginary friend, Ava, and reveals she was inspired by the real Ava he was about to ask out before deciding to play football with the friends in the storm. They come up with a theory that Ava created the disease and is using it to bring the world population down to Jacob and her, so that he can't ever choose anyone else over her. They also theorize that she made him immune by hiring the mysterious shooter to inject him with a sort of vaccination. A lab is shown revealing the real Ava working with Daniel, the mysterious shooter, to complete the formula. When he is finished, she poisons him with a glass of lemonade.One day, the three friends wake up to no sounds, no news, and no people. They were the last people alive on Earth. They decide to get an upgrade. A mysterious person, dressed as a robber, goes inside the friend's house and finds it empty. He takes off his mask to reveal Corben, a fourth alive person. He makes a sandwich and remarks that there has to be someone else out there. The friends arrive at a new, nicer house. They find no dead people inside, so they decide to stay. An envelope marked with the letter A drifts by the window.Deciding there is really no one left, they decide to go to a bakery and get some donuts. In the scene from the flash-forward plays, instead of cutting to black, the friends find Corben at a park. Excited to see another person, they talk to him and invite him over. They show him their house and invite him to stay, but he tells him he is happy with the house he moved into (the friends' old house). When Corben gets home, Ava is waiting for him. She thinks he is Jacob, but after finding out she is wrong, she recruits him and reveals that it was Jacob who engineered the disease and destroyed the cure. The friends find the letter A envelope in their backyard and read it. The letter teases that if they find all 26 envelopes in the order of the alphabet, they can find the cure and bring humanity back. They slowly find all of the envelopes, leaving only W, X, Y, and Z. One night, while looking for W, Jacob leaves to get them all some food. While out, Jacob encounters Corben and tells him about the envelopes, but Ava jumps out and kidnaps Jacob. Jacob and Corben are tied up together in a garage and are able to work out the truth that Ava is behind everything. They escape the ropes, but just before they can leave, Ava catches them. She lets Corben go but keeps Jacob. She tells him that he has to kill his friends or she will kill him. He refuses, and she leaves him locked in there, while she goes to get the envelopes. Corben gets the friends from their house, and they go to rescue Jacob but leave the house empty allowing Ava to take the envelopes. After rescuing Jacob, both the friends and Ava race to a park where they assume envelope Y and Z will be. Once at the park, they split up. Michael looks in Ava's car, Davis looks for envelopes Y and Z, and Jacob and Corben look for Ava. Jacob and Corben find Ava and confront her. Davis runs over with Y and Z, and Michael runs over empty-handed. Ava gets away, taunting them that they need all 26 envelopes to crack the code. Jacob and Corben try to go after them, but Michael stops them and reveals he had envelopes A-X in his pocket. Far away, Ava pulls over and checks her hiding place in her car. It is empty, and she knows she has lost. The friends open up the envelopes and successfully bring everyone back to life.