Mike Miller (and Phil the worm) crash land on earth, landing on (and destroying) a yacht in the middle of the ocean. He pedals to try to reach land using a tricycle floatation device over the course of many days, not reaching land. He falls asleep, despondent at the thought of never reaching land and dying at sea. He dreams about a kid version of his brother Phil needling him and telling him he can't give up. When he wakes up, he finds an apparently-abandoned boat adrift with plenty of food and water.
He eats and changes into clean clothes. The owner of the boat, Pat Brown, shows up and threatens him with a harpoon. Pat asks whether Mike has been infected with the virus. Mike explains that he was in the International Space Station for the last several years, when the virus hit. Pat introduces himself as the last man on earth.
The two men share a beer and Pat explains that when the virus hit, he bought a boat (named "Deez Knots") and has been living at sea ever since. He goes to land to get supplies every once in a while and notes that no one is immune to the virus -- land is pitch black every time he docks.
Over dinner, Pat and Mike discuss their families. Mike says that his parents and brother are in Tucson, AZ. Pat corrects him, saying "had" a family, and comments that he, too, once had a family. The two men share an expensive bottle of scotch. Mike asks Pat to take him to land. Pat tries to convince him that there is no one left, but Mike says he wants to see for himself.
Mike repeatedly catches Pat watches him while he's sleeping and starts to get nervous about the possibility of Pat killing and eating him. Pat finally agrees to take Mike to shore and to accompany him, so that Mike can see there is no one left and then rejoin Pat at sea. Pat insists that the two of them wear hazmat suits for their trip to land because Pat is convinced that they will catch the virus if they are exposed to Earth.
Mike and Pat drive around Miami in Pat's old ice cream truck, so that Mike can see there is no one left. Mike comments that he misses the noise. He wonders where all the bodies are. Pat takes him to see a bunch of bodies at a makeshift health center in a parking lot. Pat asks whether Mike still believes his family is alive and Mike is silent. Pat and Mike play a game of tennis, which Pat wins, and then begin to drive back to the boat.
On the way back, Pat spots one of Phil's "Alive in Tucson" signs on a highway exit sign. He tries to reverse before Mike can see it but Mike struggles with Pat to stop the ice cream truck and joyously runs towards the sign, commenting that he's from Tucson. Pat hits him with a wrench, knocking him out.
When Mike is knocked out, he has another hallucination where young Phil berates him for allowing Pat to hit him over the head. He tries to convince Mike to get up, threatening to pee on him for being a quitter if he doesn't get up.
Mike awakens to find Pat cleaning off the hazmat suit on the beach, near the boat. Pat tries to convince Mike that Tucson is a booby-trap by the government, to lure them there so they can cremate all the survivors and allow the people living in the bunkers to come out so they can rebuild. After a struggle in which Pat threatens to shoot him if he tries to escape, Pat hits Mike with a rock. He notices a rip in Mike's hazmat suit and breaks down crying.
Later, Mike awakens in one of the body bags at the makeshift health center that Pat had earlier taken him to. Mike takes off the hazmat suit and notices that Pat wrote "RIP Spaceman, Cause of Death: The Government" misspelled on his body bag. Mike spots a fire rescue truck and drives it towards Tucson. Back on Pat's boat, Pat talks to Mike's worm Phil, asking if it likes tennis.