Shortly after the events of the first film, a medical officer and a GEO team, equipped with video cameras, are sent into the quarantined apartment building to control the situation. After encountering some of the infected, the man from CDC uses something religious to fight them off. Surprisingly, it works. It turns out that the man from CDC is actually a priest sent by the church to get a blood sample from the Medeiros girl.

When they get to the attic, they find out that the infected can travel all around the building through the air ducts. The Medeiros girl is nowhere to be found. One of the GEO's goes up to the air duct and finds a sample of her blood - the only one that the original priest took from her. The priest then does something religious with some of it, and it explodes, confirming that it IS the blood he's looking for; however, the GEO member holding the rest of the blood drops it because of the explosion, rendering it useless. They then are forced to get the blood sample from the Medeiros girl herself.

There is a sub-plot going on while all of these events occur. Jennifer's father, who was outside getting medicine for his daughter (the infected girl from the the first film), manages to convince a firefighter to take him into the building. Now, moments before the building is quarantined , three teenagers are messing around on the roof. When the police quarantines the building, they find them and escort them back out to the street. The teenagers get back into the building through the sewage system; however, some of the firefighters see them and lock them inside so that nobody can get out through there. Inside, the teenagers find the woman's husband and the firefighter.

After a few more deaths, the two groups find each other. Then the group finds Angela Vidal - the reporter from the first movie. She has her camera with her. How she survived still remains unclear. One of the teenagers gets bitten by the infected, and so they restrain him. The priest then forces him to tell him where the Medeiros girl is, using his religious powers. The teenager (or the demon possessing him) tells him that she is "in the highest." The priest figures out that this means that she is in the attic. The chief though argues that they had already been there and they did not see anything. The demon then gives a hint that the "light" blinds them from seeing the path. When Angela was asked how she saw the Medeiros girl, she said she saw it through the Camera's Night Vision. The priest then deduced that some things can only be seen in the dark. Before leaving, they lock the teenagers in a room, probably for their protection.

Finally, they go back to the attic. When they turned on Angela's camera's night vision, a door that only appears in the dark led them to a room. Inside that room and with the lights off, they finally find the Medeiros girl. After some struggling, Angela blows her head off with a gun. The priest is enraged because he needed her, but all Angela wants to do is leave the building. At this point, the only survivors left are Angela, the priest, and a GEO member. When the priest refuses to authorize their exit, Angela starts to beat him up to force him to do so. The GEO team member tries to tell her to stop, but she eventually shoots and kills him. Then it is revealed that the Medeiros girl has already possessed Angela. She tells the priest that she doesn't really need him to get out, and then she kills him. She takes his radio and speaks through it using the priest's own voice, and says that "he" has been infected, and that the only survivor is a woman. When asked how the woman survived, Angela leaned towards the camera and smiled.

Before the credits, however, the ending of the original film is shown; when Angela gets dragged by her feet into the dark, she manages to crawl back into the camera's sight, but the Medeiros girl quickly gets on top of her. Then she inserts her tongue into Angela's mouth. When she's done, it is revealed that the tongue is really a hideous, worm-like organism that gets inside of Angela. After the whole thing is inside her, she smiles ominously. Then she hears the GEO team and the priest, and she goes into hiding, thus marking the beginning of the film.

Cast:
* Óscar Zafra as Jefe
* Jonathan Mellor as Dr.Owen
* Ariel Casas as Larra
* Alejandro Casaseca as Martos
* Pablo Rosso as Rosso
* Manuela Velasco as Ángela Vidal
* Ferran Terraza as Manu
* Javier Botet/Nico Baixas as Niña Medeiros
* Andrea Ros as Mire
* Pau Poch as Tito
* Àlex Batllori as Uri
* David Vert as Álex
* Pep Molina as Padre de Jennifer
* Claudia Font as Jennifer
* Martha Carbonell as Sra. Izquierdo
* Ana Isabel Velásquez as Chica colombiana