An act of determined protest turns chaotic when a Cambridge laboratory housing unusually aggressive chimpanzees becomes the target of a small group of animal rights activists. A scientist warns that one chimp is infected with a highly contagious virus he calls Rage, and despite the warning, an activist releases the animal. The infected chimp attacks, and within moments the woman is dead, spreading the virus rapidly across Great Britain and bringing society to its knees.
Twenty-eight days later, Jim, Cillian Murphy, a bicycle courier who had fallen into a coma after a traffic accident, awakens in St Thomas' Hospital in London to find it utterly deserted. He stumbles into empty streets, reads papers about a mass evacuation, and eventually seeks refuge in a church with the chilling proof of a brutal massacre. Infected people hunt him, but he is saved by survivors Selena, Naomie Harris, and Mark, Noah Huntley, and they bring him to safety in a small shop windowed off from the world.
At Jim's request, the trio sets out toward his parents' home in Deptford to learn what happened to his family. The journey reveals a tragedy: his parents have died by suicide during the outbreak. As dusk falls, they regroup and keep watch, and the infected slowly draw near to the quiet house. A tense moment ends with Mark being bitten, and Selena makes a difficult choice, declaring that she would do the same if the infection took hold of Jim or anyone else they care about: > if it happens to you, I'll do it in a heartbeat.
The group moves on, driven by a desperate hope for safety. They trace a beacon of light—Balfron Tower—where a makeshift signal lamp and a cab belonging to Frank, Brendan Gleeson, and his young daughter Hannah, Megan Burns, suggest a possible lead. Frank broadcasts a message of protection and “salvation from infection” from a blockade outside Manchester, inviting them to join a supposed sanctuary. The four decide to make the arduous journey together, despite Jim's misgivings.
On the road they encounter a dangerous stretch: a Tunnel crossing, wrecked vehicles, and a desperate fight for a tire change as rats and pursuing infected close in. The group uses teamwork to lever the car up and swap the tire swiftly, narrowly escaping danger and continuing toward their uncertain destination. A stop at an abandoned supermarket yields small comforts—chocolate and whiskey—in a momentary glimmer of civilization amid chaos.
Reaching Manchester, they find the blockade empty and silent. Frank's frustration boils over as he kicks a tall gate, and a drop of blood from a corpse drips into his eye, signaling the lethal spread of the infection. Soon soldiers appear and shoot him. Jim, Selena, and Hannah are taken to a heavily fortified country house under the command of Major Henry West, where they are treated to a tour and a banquet that feel more like a trap than a shelter. West reveals his brutal scheme: his broadcast was meant to lure female survivors to sustain his troops’ morale through a grim fantasy of a future for humanity. Jim and Sergeant Farrell resist, so West orders them to be shot and imprisons them.
While imprisoned, Farrell explains to Jim that the outbreak has not crossed the Atlantic and that Britain has been quarantined from the rest of the world. Jim is forced to confront a grim reality, but an opportunity presents itself when Jim manages to break free, lure away West with a siren, and release Private Mailer, an infected soldier kept chained for observation, in order to infect and kill the remaining soldiers. A tense moment unfolds as Corporal Mitchell attempts to abduct Selena, but Jim’s savage defense persuades her that he might actually be infected. Her fear almost overrides her trust, but Jim and Selena share a long, decisive kiss that reassures her of his humanity in a moment of lethal crisis.
The escape becomes a desperate chase through the country house with a standoff that ends in a brutal clash. Hannah takes action in a flash, and the trio—the now-escaped Jim, Selena, and Hannah—flee in Frank's cab. West, who has hidden in the back seat, reloads his weapon, but their escape culminates in West’s dramatic demise at the hands of the cab’s own passengers when Hannah collides the vehicle in reverse, sending Private Mailer crashing through the rear window, and Mailer’s attack rips West apart in a violent, fatal mauling as the car pulls away.
A second dawn reveals a stark, eerie aftermath. Jim recovers at a remote cottage in Cumbria while the infected lie dying of starvation on the roads. A Hawker Hunter jet sweeps overhead, and the three survivors—Jim, Selena, and Hannah—unfurl a large cloth banner spelling out the word "HELLO." They raise the banner to the sky and wave at the distant aircraft, still clinging to a fragile spark of hope for a world beyond the quarantine, asking whether anyone listening in the outside world might still see them.